Sexually transmitted Infections

Learning objectives: At the end of this lesson students are expected to

1. Define Sexually transmitted diseases ( STDs or STIs )
2. Understand the common etiologic agent for STIs
3. Understand the epidemiology of different STIs
4. Describe the pathophysiology of common STIS
5. Identify the clinical manifestations of different STIs
6. List the complications and Organ systems affected by STIs
7. Describe the most commonly investigations for the diagnosis of STIs
8. Make an appropriate diagnosis of Different STIs
9. Understand the syndromic approach for the management of different STIs

Introduction to STI
sexually transmitted diseases (STD), also referred to as sexually transmitted infections (STI)
and venereal
diseases (VD),
are
illnesses
that
have
a
significant
probability
of transmission between humans by means of sexual behavior, including vaginal intercourse, anal
sex and oral sex. Some STIs can also be contracted by using IV drug needles after their use by an
infected person, as well as through any incident involving the contact of a wound with contaminated
blood or through childbirth or breastfeeding.
Not all STIs are symptomatic, and symptoms may not appear immediately after infection. In some
instances a disease can be carried with no symptoms, which leaves a greater risk of passing the disease
on to others. Bacterial STIs include chlamydia, gonorrhea, andsyphilis. There are several viral STIs
including herpes simplex, HIV, and human papillomavirus (HPV). There is also parasite STIs,
including the crab louse.
Safer sex is a method of decreasing the risk of contracting sexually transmitted infections during sexual
activity. Prevention is key in addressing incurable STIs, such as HIV and herpes. The most effective
way to prevent sexual transmission of STIs is to avoid contact of body parts or fluids which can lead to
transfer with an infected partner. Not all sexual activities involve contact: cybersex,
phonesex or masturbation from a distance are methods of avoiding contact. Proper use
of condoms reduces contact and risk. Vaccines are available that protect against some viral STIs, such
as Hepatitis B, and some types of HPV.
There are 19 million new cases of sexually transmitted infections every year in the United States, and,
in 2005, the World Health Organization estimated that 448 million people aged 1549 were being
infected a year with curable STIs (such as syphilis,gonorrhea and chlamydia). Sexually
transmitted infections have been well known for hundreds of years, and venereology is the branch
1

of medicine that studies these diseases. While in the past, these illnesses have mostly been referred to
as STDs or VD, the term sexually transmitted infections (STIs) is currently preferred, as it has a
broader range of meaning; a person may be infected, and may potentially infect others, without having
a disease.
Until the 1990s, STIs were commonly known as venereal diseases, the word venereal being derived
from the Latin word venereus, and meaning relating to sexual intercourse or desire, ultimately derived
from Venus, the Roman goddess of love Social disease was a phrase used as a euphemism.
Sexually transmitted infection is a broader term than sexually transmitted disease. An infection is
colonization by a parasitic species, which may not cause any adverse effects. In a disease, the infection
leads to impaired or abnormal function. In either case, the condition may not exhibit signs or symptoms.
Increased understanding of infections like HPV, which infects a significant portion of sexually active
individuals but cause disease in only a few has led to increased use of the term STI. Public
health officials originally introduced the term sexually transmitted infection, which clinicians are
increasingly using alongside the term sexually transmitted disease in order to distinguish it from the
former.
STD may refer only to infections that are causing diseases, or it may be used more loosely as a
synonym for STI. Most of the time, people do not know that they are infected with an STI until they
are tested or start showing symptoms of disease. Moreover, the term sexually transmissible disease is
sometimes used since it is less restrictive in consideration of other factors or means of transmission. For
instance,meningitis is transmissible by means of sexual contact but is not labeled an STI because sexual
contact is not the primary vector for the pathogens that cause meningitis. This discrepancy is addressed
by the probability of infection by means other than sexual contact. In general, an STI is an infection
that has a negligible probability of transmission by means other than sexual contact, but has a realistic
means of transmission by sexual contact (more sophisticated meansblood transfusion, sharing
of hypodermic needlesare not taken into account). Thus, one may presume that, if a person is infected
with an STI, e.g., chlamydia, gonorrhea, genital herpes, HPV it was transmitted to him/her by means
of sexual contact.
The diseases on this list are most commonly transmitted solely by sexual activity. Many infectious
diseases, including the common cold, influenza, pneumonia, and most others that are transmitted
person-to-person can also be transmitted during sexual contact, if one person is infected, due to the close
contact involved. However, even though these diseases may be transmitted during sex, they are not
considered STIs.
Sign and symptoms
Not all STIs are symptomatic, and symptoms may not appear immediately after infection. In some
instances a disease can be carried with no symptoms, which leaves a greater risk of passing the disease
on to others. Depending on the disease, some untreated STIs can lead to infertility, chronic pain or even
death.
Cause
Transmission

The risks and transmission probabilities of sexually transmitted diseases :

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Bacterial

Chancroid (Haemophilus ducreyi)

Chlamydia (Chlamydia trachomatis)
Gonorrhea (Neisseria gonorrhoeae), colloquially known as "the clap"
Granuloma inguinale or (Klebsiella granulomatis)
Syphilis (Treponema pallidum)
Fungal
Candidiasis (yeast infection)
Viral
Viral
hepatitis (Hepatitis
B
virus)saliva,
venereal
fluids.
(Note: Hepatitis A and Hepatitis E are transmitted via the fecal-oral route; Hepatitis C is rarely sexually
transmittable,[20] and the route of transmission of Hepatitis D (only if infected with B) is uncertain,
but may include sexual transmission.[21][22][23])
Herpes simplex (Herpes simplex virus 1, 2) skin and mucosal, transmissible with or without visible
blisters
HIV (Human Immunodeficiency Virus)venereal fluids, semen, breast milk, blood
HPV (Human Papillomavirus)skin and mucosal contact. 'High risk' types of HPV cause almost
all cervical cancers, as well as someanal, penile, and vulvar cancer. Some other types of HPV
cause genital warts.
Molluscum contagiosum (molluscum contagiosum virus MCV)close contact
Parasites
Crab louse, colloquially known as "crabs" or "pubic lice" (Pthirus pubis)
Scabies (Sarcoptes scabiei)
Protozoal
Trichomoniasis (Trichomonas vaginalis), colloquially known as "trich"
Main types

Sexually transmitted infections include:

Chlamydia is a sexually transmitted infection caused by the bacterium Chlamydia trachomatis. In
women, symptoms may include abnormal vaginal discharge, burning during urination, and bleeding in
between periods, although most women do not experience any symptoms. Symptoms in men include pain
when urinating, and abnormal discharge from their penis. If left untreated in both men and women,
Chlamydia can infect the urinary tract and potentially lead to pelvic inflammatory disease (PID). PID
can cause serious problems during pregnancy and even has the potential to cause infertility. It can cause
a woman to have a potentially deadly ectopic pregnancy, in which the child is born outside of the uterus.
However, Chlamydia can be cured with antibiotics.
The two most common forms of herpes are caused by infection with herpes simplex virus (HSV).
HSV-1 is typically acquired orally and causes cold sores; HSV-2 is usually acquired during sexual
contact and affects the genitals, and however either strain may affect either site.[26] Some people are
asymptomatic or have very mild symptoms. Those that do experience symptoms usually notice them 2 to
20 days after exposure which last 2 to 4 weeks. Symptoms can include small fluid-filled blisters,
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headaches, backaches, itching or tingling sensations in the genital or anal area, and pain during
urination, Flu like symptoms, swollen glands, or fever. Herpes is spread through skin contact with a
person infected with the virus. The virus affects the areas where it entered the body. This can occur
through kissing, vaginal intercourse, oral sex or anal sex. The virus is most infectious during times
when there are visible symptoms; however those who are asymptomatic can still spread the virus
through skin contact. The primary attack is the most severe because the body does not have any
antibodies built up. After the primary attack, one might have recurring attacks that are milder or might
not even have future attacks. There is no cure for the disease but there are antiviral medications that
treat its symptoms and lower the risk of transmission (Valtrex). Although HSV-1 is typically the "oral"
version of the virus and HSV-2 is typically the "genital" version of the virus, a person with HSV-1
orally CAN transmit that virus to their partner genitally. The virus, either type, will settle into a
nerve bundle either at the top of the spine, producing the "oral" outbreak, or a second nerve bundle at
the base of the spine, producing the genital outbreak.
The human papillomavirus (HPV) is the most common STI in the United States. There are more than
40 different strands of HPV and many do not cause any health problems. In 90% of cases the bodys
immune system clears the infection naturally within 2 years. Some cases may not be cleared and can
lead to genital warts (bumps around the genitals that can be small or large, raised or flat, or shaped like
cauliflower) or cervical cancer and other HPV related cancers. Symptoms might not show up until
advanced stages. It is important for women to get pap smears in order to check for and treat cancers.
There are also two vaccines available for women (Cervarix andGardasil) that protect against the types
of HPV that cause cervical cancer. HPV can be passed through genital-to-genital contact as well as
during oral sex. It is important to remember that the infected partner might not have any symptoms.
Gonorrhea is caused by bacterium that lives on moist mucous membranes in the urethra, vagina,
rectum, mouth, throat, and eyes. The infection can spread through contact with the penis, vagina,
mouth or anus. Symptoms of Gonorrhea usually appear 2 to 5 days after contact with an infected
partner however, some men might not notice symptoms for up to a month. Symptoms in men include
burning and pain while urinating, increased urinary frequency, discharge from the penis (white, green,
or yellow in color), red or swollen urethra, swollen or tender testicles, or sore throat. Symptoms in
women may include vaginal discharge, burning or itching while urinating, painful sexual intercourse,
severe pain in lower abdomen (if infection spreads to fallopian tubes), or fever (if infection spreads to
fallopian tubes), however many women do not show any symptoms. There are some antibiotic resistant
strains for Gonorrhea but most cases can be cured with antibiotics.
Syphilis is an STI caused by a bacterium. If acquired, syphilis needs to be treated adequately, otherwise

it can cause long-term complications and death. Clinical manifestations of syphilis include the
ulceration of the uro-genital tract, mouth or rectum; if left untreated the symptoms worsen. In recent
years, the prevalence of syphilis has declined in Western Europe, but it has increased in Eastern
Europe (former Soviet states). A high incidence of syphilis can be found in places such
as Cameroon, Cambodia, Papua New Guinea.

Trichomoniasis is a common STI that is caused by infection with a protozoan parasite

called Trichomonas vaginalis. Trichomoniasis affects both women and men, but symptoms are more
common in women. Most patients are treated with an antibiotic called metronidazole, which is very
effective.
HIV (human immunodeficiency virus) damages the body's immune system which interferes with
fighting off disease-causing agents. The virus kills CD4 cells, which are white blood cells that help fight
off various infections. HIV is carried in body fluids, and is spread by sexual activity. It can also be
spread by contact with infected blood, breast feeding, childbirth, and from mother to child during
pregnancy When HIV is at its most advanced stage, an individual is said to have AIDS (acquired
immunodeficiency syndrome). There are different stages of the progression of and HIV infection. The
stages include primary infection, asymptomatic infection, symptomatic infection, and AIDS. In the
primary infection stage, an individual will have flu like symptoms (headache, fatigue, fever, muscle
aches) for about 2 weeks. In the asymptomatic stage, symptoms usually disappear, and the patient can
remain asymptomatic for years. When HIV progresses to the symptomatic stage, the immune system is
weakened, and has a low cell count of CD4+ T Cells. When the HIV infection becomes life-threatening,
it is called AIDS. People with AIDS fall prey to opportunistic infections and die as a result. When the
disease was first discovered in the 1980s, those who had AIDS were not likely to live longer than a few
years. There are now antiretroviral drugs (ARVs) available to treat HIV infections. There is no
known cure for HIV or AIDS but the drugs help suppress the virus. By suppressing the amount of
virus in the body, people can lead longer and healthier lives. Even though their virus levels may be low
they can still spread the virus to others.
Unscreened

There are many species of bacteria, protozoa, fungi, and viruses, many which remain undocumented or
poorly studied with regards to sexual transmission. Despite that the above include what are generally
known as STIs, sexually transmission of microbes is far from limited to the above list. Since the sexual
route of transmission is not considered common, and/or the microbe itself is not implicated in a major
research study on disease, the following pathogens are simply not screened for in sexual health clinics.
Some of these microbes are known to be sexually transmittable.
Microbes known to be sexually transmissible (but not generally considered STDs/STIs) include:
Ebola- transmissible 2 months after recovery.
Marburg virus - Virus in semen for 7 weeks after clinical recovery.
HTLV (both types 1 and 2) - Sexually transmissible, consumption of breast milk breastfeeding, and once
mistaken as a HIV, risk of leukemia.
Pathophysiology

Many STIs are (more easily) transmitted through the mucous membranes of
the penis, vulva, rectum, urinary tract and (less oftendepending on type of infection)
the mouth,throat, respiratory tract and eyes. The visible membrane covering the head of the
penis is a mucous membrane, though it produces no mucus (similar to the lips of the mouth). Mucous
membranes differ from skin in that they allow certain pathogens into the body.[43] The amount of
contact with infective sources which causes infection varies with each pathogen but in all cases a
5

disease may result from even light contact from fluid carriers like venereal fluids onto a mucous
membrane.
This is one reason that the probability of transmitting many infections is far higher from sex than by
more casual means of transmission, such as non-sexual contacttouching, hugging, shaking handsbut
it is not the only reason. Although mucous membranes exist in the mouth as in the genitals, many
STIs seem to be easier to transmit through oral sex than through deep kissing. According to a safe sex
chart, many infections that are easily transmitted from the mouth to the genitals or from the genitals to
the mouth are much harder to transmit from one mouth to another. With HIV, genital fluids happen
to contain much more of the pathogen than saliva. Some infections labeled as STIs can be transmitted
by direct skin contact. Herpes simplex and HPV are both examples. KSHV, on the other hand, may be
transmitted by deep-kissing but also when saliva is used as a sexual lubricant.
Depending on the STI, a person may still be able to spread the infection if no signs of disease are
present. For example, a person is much more likely to spread herpes infection when blisters are present
than when they are absent. However, a person can spread HIV infection at any time, even if he/she
has not developed symptoms of AIDS.
All sexual behaviors that involve contact with the bodily fluids of another person should be considered
to contain some risk of transmission of sexually transmitted diseases. Most attention has focused on
controlling HIV, which causes AIDS, but each STI presents a different situation.
As may be noted from the name, sexually transmitted diseases are transmitted from one person to
another by certain sexual activities rather than being actually caused by those sexual
activities. Bacteria, fungi, protozoa or viruses are still the causative agents. It is not possible to catch
any sexually transmitted disease from a sexual activity with a person who is not carrying a disease;
conversely, a person who has an STI got it from contact (sexual or otherwise) with someone who had
it, or his/her bodily fluids. Some STIs such as HIV can be transmitted from mother to child either
during pregnancy or breastfeeding.
Although the likelihood of transmitting various diseases by various sexual activities varies a great deal,
in general, all sexual activities between two (or more) people should be considered as being a two-way
route for the transmission of STIs, i.e., "giving" or "receiving" are both risky although receiving
carries a higher risk.
Healthcare professionals suggest safer sex, such as the use of condoms, as the most reliable way of
decreasing the risk of contracting sexually transmitted diseases during sexual activity, but safer sex
should by no means be considered an absolute safeguard. The transfer of and exposure to bodily fluids,
such as blood transfusions and other blood products, sharing injection needles, needle-stick injuries
(when medical staff are inadvertently jabbed or pricked with needles during medical procedures),
sharing tattoo needles, and childbirth are other avenues of transmission. These different means put
certain groups, such as medical workers, and haemophiliacs and drug users, particularly at risk.
Recent epidemiological studies have investigated the networks that are defined by sexual relationships
between individuals, and discovered that the properties of sexual networksare crucial to the spread of

sexually transmitted diseases. In particular, assortative mixing between people with large numbers of
sexual partners seems to be an important factor.
It is possible to be an asymptomatic carrier of sexually transmitted diseases. In particular, sexually
transmitted diseases in women often cause the serious condition of pelvic inflammatory disease.
Prevention
Safe sex

Prevention is key in addressing incurable STIs, such as HIV and herpes. Sexual health
clinics promote the use of condoms and provide outreach for at-risk communities.
The most effective way to prevent sexual transmission of STIs is to avoid contact of body parts or
fluids which can lead to transfer with an infected partner. Not all sexual activities involve
contact: cybersex, phone sex or masturbation from a distance are methods of avoiding contact.
Proper use of condoms reduces contact and risk. Although a condom is effective in limiting exposure,
some disease transmission may occur even with a condom.
Both partners should get tested for STIs before initiating sexual contact, or before resuming contact if a
partner engaged in contact with someone else. Many infections are not detectable immediately after
exposure, so enough time must be allowed between possible exposures and testing for the tests to be
accurate. Certain STIs, particularly certain persistent viruses like HPV, may be impossible to detect
with current medical procedures.
Many diseases that establish permanent infections can so occupy the immune system that other diseases
become more easily transmitted. The innate immune system led by defensins against HIV can
prevent transmission of HIV when viral counts are very low, but if busy with other viruses or
overwhelmed, HIV can establish itself. Certain viral STI's also greatly increase the risk of death for
HIV infected patients.
Vaccines

Vaccines are available that protect against some viral STIs, such as Hepatitis A, Hepatitis B, and
some types of HPV. Vaccination before initiation of sexual contact is advised to assure maximal
protection.
Condoms

Condoms and female condoms only provide protection when used properly as a barrier, and only to
and from the area that it covers. Uncovered areas are still susceptible to many STDs.
In the case of HIV, sexual transmission routes almost always involve the penis, as HIV cannot spread
through unbroken skin, thus properly shielding the insertive penis with a properly worn condom from
the vagina or anus effectively stops HIV transmission. An infected fluid to broken skin borne direct
transmission of HIV would not be considered "sexually transmitted", but can still theoretically occur
during sexual contact, this can be avoided simply by not engaging in sexual contact when having open
bleeding wounds.
Other STIs, even viral infections, can be prevented with the use of latex, polyurethane or polyisoprene
condoms as a barrier. Some microorganisms and viruses are small enough to pass through the pores in
natural skin condoms, but are still too large to pass through latex or synthetic condoms.
7

Proper usage entails:

Not putting the condom on too tight at the end, and leaving 1.5 cm (3/4 inch) room at the tip
for ejaculation. Putting the condom on snug can and often does lead to failure.
Wearing a condom too loose can defeat the barrier.
Avoiding inverting, spilling a condom once worn, whether it has ejaculate in it or not.
Avoiding the use of oil based lubricants (or anything with oil in it) with latex condoms, as oil can eat
holes into them.
Using flavored condoms for oral sex only, as the sugar in the flavoring can lead to yeast infections if
used to penetrate.
Not following the first five guidelines above perpetuates the common misconception that condoms are
not tested or designed properly.
In order to best protect oneself and the partner from STIs, the old condom and its contents should be
assumed to be infectious. Therefore the old condom must be properly disposed of. A new condom should
be used for each act of intercourse, as multiple usage increases the chance of breakage, defeating the
effectiveness as a barrier.
Nonoxynol-9

Researchers had hoped that nonoxynol-9, a vaginal microbicide would help decrease STI risk. Trials,
however, have found it ineffective[46] and it may put women at a higher risk of HIV infection.
Screening

Sexually active women under the age of 25 and those over 25 with risk should be screened for chlamydia
and gonorrhea yearly After being treated for gonorrhea all people should be re tested for the disease
after three months.
Nucleic acid amplification tests are the recommended method of diagnosis for gonorrhea and
chlamydia. This can be done on either urine in both men and women, vaginal or cervical swabs in
women, or urethral swabs in men.
Diagnosis

Testing may be for a single infection, or consist of a number of tests for a range of STIs, including
tests for syphilis, trichomonas, gonorrhea, chlamydia, herpes, hepatitis andHIV. No procedure tests
for all infectious agents.
STI tests may be used for a number of reasons:
as a diagnostic test to determine the cause of symptoms or illness
as a screening test to detect asymptomatic or presymptomatic infections
as a check that prospective sexual partners are free of disease before they engage in sex without safer
sex precautions (for example, when starting a long term mutually monogamous sexual relationship,
in fluid bonding, or for procreation).
as a check prior to or during pregnancy, to prevent harm to the baby
as a check after birth, to check that the baby has not caught an STI from the mother
to prevent the use of infected donated blood or organs
as part of the process of contact tracing from a known infected individual
as part of mass epidemiological surveillance
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Early identification and treatment results in less chance to spread disease, and for some conditions may
improve the outcomes of treatment. There is often a window period after initial infection during
which an STI test will be negative. During this period the infection may be transmissible. The
duration of this period varies depending on the infection and the test. Diagnosis may also be delayed by
reluctance of the infected person to seek a medical professional. One report indicated that people turn to
the Internet rather than to a medical professional for information on STIs to a higher degree than for
other sexual problems.
Managment
High-risk exposure such as that which occurs in rape cases may be treated preventatively using
antibiotic combinations such as azithromycin, cefixime, and metronidazole.
An
option
for
treating
partners
of
patients
(index
cases)
diagnosed
with chlamydia or gonorrhea is patient-delivered partner therapy, which is the clinical practice of
treating the sex partners of index cases by providing prescriptions or medications to the patient to take
to his/her partner without the health care provider first examining the partner.
Definition
Sexually transmitted diseases (STDS) are a diverse group of infections, caused by different types of
microbial agents, that are frequently transmitted by sexual contact, and for which sexual transmission
is epidemiologically important, are considered sexually transmitted diseases. Sexual includes the full
range of heterosexual or homosexual behavior, including genital, oral-genital, oral-anal, and genitalanal contact.
At present there are more than 20 known causes of STD. No single STD can be regarded as an
isolated problem because multiple infections are common and because the presence of one STD denotes
high-risk sexual behavior that is often associated with other, more serious infection.
Most STDs are rarely if ever transmitted by fomites, food, flies, or casual contact.
At least one sexual partner is always infected; the apparent exceptions usually can mbe attributed to
prolonged sub-clinical infection in one or both partners. Therefore, risk assessment (including
elicitation of a sexual history) and management of sexual partners are of paramount importance.
Epidemiology of STIs
STIs are major public health problems in all countries, but are especially in developing countries
where access to adequate diagnostic and treatment facilities is very limited or nonexistent. There is
limited information on the incidence and prevalence of STIs is Internal Medicine Ethiopia. FMOH
compiled 58,632 and 27,947cases from all regions in 2002 and 2003 respectively.
A large proportion of STIs are symptomatic and most symptomatic patients seek treatment from
traditional healers , pharmacists , drug vendor shops and market places
STDs can be classified and managed in two different ways ( approaches )
1. Etiologic approach

 Advantages: Accurate diagnosis, accurate treatment, proper use of antibiotics (decreases over
treatment and antibiotic resistance). It is the better way to diagnose and treat asymptomatic infections
Disadvantages: Needs lab support and expertise, expensive (cost may be incurred due to lab tests )
and it is time consuming
2. Syndromic approach
Advantages: Treatment can be given immediately, mixed infection may exist and may be adrsessed,
there is no need for laboratory diagnosis and the treatment can be given by middle level health
professionals. Hence this approach may be a good alternative for in resource limited settings.
Disadvantages: over treatment with antibiotics, there is risk of creating antibiotic resistance and
decreased compliance. There is also increased cost of drugs.
Moreover asymptomatic infection missed.
N.B In general, an overall approach to the management of a patient with sexually transmitted disease
begins with
Risk assessment of:
Sexual orientation and practice
Number of recent and current sexual partners
History of STD in the patient
Recent history of STD of the partner
Sociodemographic and other markers of high risk
Clinical assessment: elicitation of information on specific current symptoms and signs of STDs.
Laboratory tests: If available, confirmatory diagnostic or screening tests may then be ordered. Internal
Medicine
Comprehensive Case Management: is vital approach for controlling STIs. So health care providers
should undertake the following measures besides treating individual patients
1. Partner notification and management
2. Condom promotion and supply
3. Health education and risk reduction counseling
4. Linkage with HIV counseling and testing
5. Follow-up visits for patients with STI
STI Syndromes

Urethral discharge Syndrome

Vaginal discharge
Genital ulcer
Inguinal bubo
Scrotal swelling
Lower abdominal pain
Neonatal conjunctivitis
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1. Urethral discharge:
Urethral discharge is the most common presenting compliant of men with STD. In urethral discharge,
exudate is present in the anterior urethra and the discharge is often accompanied by dysuria or
urethral discomfort. It may lead to epididymitis and complications such as infertility and urethral
stricture.
Etiology
For practical purposes, STD-related urethritis is divided into
Gonococcal urethritis: caused by Nisseria gonorrhea

Has a short incubation period (2-3days

Vast majority of cases present with abundant and purulent discharge
Tend to produce more severe urinary tract infection symptoms like
dysuria, urgency and frequency.

Nongonococcal urethritis (NGU): usually caused by Chlamydia trachomatis or U.urealyticum.

Has scanty to moderate, white, mucoid or serous discharge.
Mild urinary tract infection symptoms
Has long incubation period (1-3 weeks). Internal Medicine
The quantity and appearance of the discharge can be used to distinguish accurately gonococcal and
nongonococcal urethritis in about 75-80% of patients who have not urinated recently. It cant, of
course, be used to diagnose dual infection with N.gonorrhea and C.trachomatis. Milking of the urethra
may be necessary to get a good amount of discharge sample.
Laboratory
Microscopy of urethral discharge stained with methylene blue or safranin or Grams stain shows pus
cells with characteristic intracellular coffee bean shaped diplococci N.gonorrhea.

Pus cells without intracellular diplococci = NGU.

Treatment:
When the accurate etiologic diagnosis is made
Gonococcal Urethritis:
Ceftriaxone 250mg IM stat OR Ciprofloacin 500mg PO stat OR Spectinomycin 2mg IM
stat.
NGU: Doxycycline 100mg PO BID for 7 days or Tetracycline 500mg PO QID for 7 days
OR Erythromycin 500mg PO QID for 7 days if the patent has contraindication for TTC..
When there is no Etiologic diagnosis: Treatment should cover both gonococccal and chlamydial
infections (combine the above treatments)
2. Vaginal Discharge:
Etiology
1. N.gonorrhea
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2. Chlamydia trachomatis
3. Trichomonas vaginalis,
4. Gardnerella vaginalis
5. Candida albicans
6. Vaginal anaerobes (bacteria vaginosis)
The first three are sexually acquired and the last three are endogenous infections.
The first two cause cervicitis while the last four cause vaginitis. Internal Medicine
Bacterial vaginosis (Gardnerella vaginalis) is the leading cause of vaginal discharge in Ethiopia
followed by Candidiasis, Trichomoniasis, and Gonococcal and Chlamydial cervicitis.
As urethritis in males, co-infection with C.trachomatis is common in women with gonorrhea (~ 50%).
Clinical feature
Many women have a small amount of vaginal discharge (physiologic leukorrhea), which is clear and
odourless. It becomes abnormal if the woman notes a change in the amount , colour or odour of the
discharge . In general, most women with this syndrome will complain of:
o
o
o
o
o

Excessive secretions and soiling of undergarments

Changes in colour and/or odour of discharge
Associated itching, dysuria, dysparunia
Redness of vulva
Sometimes may be accompanied by lower abdominal pain

The initial assessment of a patient who has vaginal discharge includes risk assessment and clinical
evaluation with speculum examination to determine the site of infection.
Vaginitis: bacterial vaginosis, vaginal candidiasis and /or trichomoniasis are the usual causes of
vaginitis.
Bacterial vaginosis and trichomoniasis are more frequent among sexually active women while
vaginal candidiasis occurs when there is impairment of local or systemic defense mechanism.
The discharge in bacterial vaginosis is homogenous with a typical fishy odour due to the presence of
volatile amines and this may e apparent during examination or when the discharge is mixed with 10 %
KOH.
Trichomonads present with profuse, runny, mal-odorous discharge. Yeasts (Candida) often present
with white, curd-like discharge and pruritus.
Speculum examination: in isolated vaginitis the cervix looks healthy and discharge is not coming from
the cervical opening.

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Cervicitis: The presence of purulent exudates from the cervical os indicates infection with
N.gonorrhea and C.trachomatis.
Risk factors for STI related cervicitis in Ethiopia ( one or more of the following )

Multiple sexual partners in the last 3 months Internal Medicine

New sexual partners in the last 3 months
Age less than 25 years
Having ever traded sex Cervicitis is frequently asymptomatic. It may be detected on
routine pelvic examination or during evaluation of a patient with vaginal discharge

Complications of Cervicitis and Vaginitis

o
o
o
o
o

PID
Premature rapture of membrane
Preterm labour
Infertility
Chronic pelvic pain

Laboratory:
It is used mainly for the diagnosis of trichomoniasis, bacterial vaginosis and candidiasis
T.vaginalis: characteristic jerky motility of the parasite with many leukocytes.
B.vaginosis:
o The typical fishy odour will be enhanced by the addition of 1- 2 drops of KOH to the
specimen of vaginal discharge (sniff test)
o Number of epithelial cells per microscopic field exceeds the number of leukocytes.
o Clue cells =cornified squamous epithelial cells covered by coccobacilli.
Candidiasis: Look for yeast (10% KOH may improve diagnostic sensitivity).
N.B. In general, Gram stains are not helpful in diagnosing gonorrhea in females (low sensitivity).
Treatment
When accurate Diagnosis is made
T.vaginalis : Metronidazole 2gm PO stat
B. Vaginosis
Only symptomatic women need treatment.
Metronidazole 500mg PO BID for 7 days or Metronidazole 2 gm as single dose and repeat after
48hr.
Vulvovaginal candidiasis

13

Topical antifungal agents: Nystatin 100,000-1,000,000 IU, intravaginally daily for 14 days.
Miconazole or clotrimazole 200mg intravaginally daily for 3 days
Mucopurulent discharge from the cervix : treat for gonorrhea and chlamydial infection. Internal
Medicine
When Specific diagnosis could not be made manage as vaginal discharge syndrome
Recommended treatment for Vaginal Discharge
Risk Assessment Positive Risk Assessment Negative
Ciprofloxacin 500 mg PO stat Or Spectinomycin 2gm IM stat Plus Doxycycline 100 mg PO BID for
7 days Plus Metronidazole 500mg Po ID for 7 days
Metronidazole 500mg Po ID for 7 days Plus Clotrimazole vaginal tabs 200mg at bed time for 3 days
3. Genital Ulcer:
A genital ulcer is a loss of continuity of the skin of the genitalia.
Genital ulcers may be painful or painless and are frequently accompanied by inguinal
lymphadenopatly.
Common Etiology agents:
Treponema pallidum (syphilis)
Haemophilus ducreyi (chancroid)
Calymmatobacterium granulomatis (granuloma inguinale)
C.trachomatis serovar L1-L3 (Lymphogranuloma venereum or LGV)
Herpes virus 1 or 2 (Herpes simplex virus or HSV)
Syphilis
Genital ulcer occurs in the primary stage of the diseases
It starts as a small popular lesion that rapidly ulcerates to produce a non tender indurated lesion with
a clean base and raised margins known as chancre
Chancres may appear at any point of contact :genitals, anus, mouth, lips
Heal without treatment in 1 to 6 weeks
Swollen lymph nodes may appear Internal Medicine
Complications
o Secondary syphilis
14

o Aortitis with valvulitis

o Neurosyphilis
Genital Herpes:
HSV virus has two types
o HSV-2 causes dominantly genital disease
o HSV-1 causes dominantly oral disease
Worldwide the most common cause of genital ulcer
Latency and frequent recurrence characterizes genital herpes , producing a lifelong
/persistent

infection

Herpetic ulcers

Are usually painful and multiple

Starts as clear vesicle and becomes pustule, which later erodes to an ulcer and then crusts
Heals spontaneously after 2-3 weeks
Recurrence possible but milder (number of vesicles are fewer)

It tends to be aggressive in HIV patients with extensive tissue involvement and chronic ulceration.
It may also be dissemination to CNS, skin etc
Complications:
o Recurrence
o Aseptic meningitis and enchephalitis
Chancroid
Caused by Haemophilus ducreyi
Is one of the commonest causes of genital ulcer in most developing countries, however it was not
found to be a common cause of genital ulcer in Ethiopia.
Incubation period: 3 -15 days
Ulcer on the penile shaft or prepuce
It is painful progressing from a small papule to pustule and then ulcer with soft margins described as
soft chancre , yellow gray exudative covering and erythema
Inguinal adenopathy that becomes necrotic and fluctuant ( bubo ) follows the ulcer within 1-2 weeks
Complication: penile autoamputaion Internal Medicine
Lymphogranuloma Venereum (LGV)
15

 Caused by L1, L2 and L3 serovars of Chlamydia trachomatis

There is little evidence on the prevalence of LGV in Ethiopia
Major pathology occurs in the lymphatic system
Primary stage is marked by a painless vesiculo-papular ulceration at the site of inoculation
Located in the penis in men
On the labia and posterior vagina in women.
Primary lesion usually not noticed.
The secondary stage is described as the inguinal syndrome
A painful inguinal lymphadenitis with constitutional symptoms
In men infection usually spreads through the lymphatics causing inguinal and femoral
lymphadenitis.
In women upper vaginal and cervical infection results in enlargement of the obturator and iliac
nodes. (sometimes pelvic nodes)
Inguinal adenopathy is usually unilateral (2/3 of cases)
Nodes initially discreet later becomes fluctuant and suppurative developing multiple draining fistulas
Bubo may be grooved by the inguinal ligament ("groove sign" of LGV)
External genitalia may be oedematous and swollen
May lead to anatomical distortion and irregularity, particularly of the penis
Spontaneous healing after several months possible
Late complications include
Genital elephantiasis
Adhesion
Stricture and fistula of the penis, urethra and the rectum
Granuloma Inguinale (Donovanosis)
Chronic: progressively destructive bacterial infection of the genital region without
symptoms

systemic

Etiology: Calymmatobacterium granulomatis a gram-negative intra-cellular bacteria

Transmission sexual and non-sexual contact Internal Medicine
Distribution mainly in Australia, Caribbean, India, and southern Africa. Little information about
its prevalence in Ethiopia
16

Clinical Manifestation
Incubation period usually1 to 4 weeks may be as long as a year
The patient usually presents with a non suppurative genital lesion which develops from a small firm
papule to painless ulcer with a beefy-red appearance and non-purulent base
Lesion bleeds easily, expand gradually
Extra inguinal in 6% of cases
50% women have lesion on cervix
Complications
o Genital pseudo-elephantiasis of labia
o Adhesion
o Urethral , vaginal or rectal stenosis
Management of Genital Ulcer
1. When specific Etiologic diagnosis is made
Syphilis:
Benzanthine penicillin 2.4million IU IM stat OR
Procaine penicillin 1.2million IU daily IM for 10 days.
In penicillin allergic patients, doxycycline 100mg PO BID for 15 days or Tetracycline 500mg
PO QID for 15 days.
Genital Herpes:
Acyclovir 200 mg 5X per day for 10 days or Acyclovir 400 mg Po TID for 10 days
Treatment of chancroid:
Ceftriaxone 250mg 1M stat or
Erythromycin 500mg PO TID for 7 days
Treatmen of LGV:
Doxycycline 100mg PO BID for 14 days or
Tetracycline 500mg PO QID for 14 days
Treatment of Granuloma inguinale

17

 Cotrimoxazole 02 tab PO BID for 14 days

N.B Tetracycline is contraindicated during pregnancy Internal Medicine
2. When specific Etiologic diagnosis is not made Syndromic approach
Recommended treatment for non-vesicular genital ulcer
Benzanthine penicillin 2.4million IU IM stat
Or (in penicillin allergic patients)
Doxycycline 100mg PO BID for 14 days
Plus Ciprofloxacin 500 mg PO for 3 days or
Erythromycin 500mg PO QID for 7 days
Recommended treatment for Vesicular, multiple or recurrent genital ulcer
Acyclovir 200 mg 5X per day for 10 days or
Acyclovir 400 mg Po TID for 10 days
Recommended treatment for Recurrent Infection: Acyclovir 400 mg Po TID for 5 days
Suppressive therapy: Acyclovir 400 mg PO BID continuously
4. Lower abdominal pain:
Lower abdominal pain in women is associated with pelvic inflammatory disease (PID).PID denotes
pelvic infections in women (e.g. salphingitis, endometritis, parametritis, oopheritis) caused by
microorganisms which generally ascend from the lower genital tract to invade the
endometrium, fallopian tubes, ovaries, other adjacent tissues and peritoneum
Etiology:
Commonly N.gonorrhea and C.trachomatis which are sexually transmitted
PID if often polymicrobial and may be associated with Mycoplasma , Bacteriods , Streptococcus ,
E.Coli , H .Influenza which may or may not be sexually transmitted
Risk factors:
The occurrence of vaginal discharge may be an antecedent event
STD
postpartum and postabortal ascending infections
Intra uterine device ( IUD) Internal Medicine

18

Clinical feature:
Mild to severe bilateral lower abdominal pain is the most common complaint, which may first be
noticed during or shortly after the menses and which is sometimes associated with fever.
The presence of vaginal discharge supports the diagnosis of PID and pain during intercourse or
urination may also be present
Physical examination
Lower abdominal and adenexal tenderness together with cervical excitation tenderness may be
indicative of PID.
A tender pelvic mass together with fever, nausea or vomiting can also be detected.
Vaginal discharge, genital ulcer, presence of IUD, open cervix (abortion tissue seen or felt) support
the diagnosis of PID.
Diagnosis:
Is often difficult. Over diagnosis and treatment may be justified in order to prevent complications.
Rule out other cause of lower abdominal pain in women such as appendicitis , ectopic pregnancy and
Cholecystitis
Laboratory: Direct wet mount microscopy of a vaginal specimen is necessary. The presence of pus cells
in numbers exceeding those of epithelial cells suggests infection of the lower genital tract.
Complications
Peritonitis and intra-abdominal abscess
Adhesion and Intestinal obstruction
Ectopic Pregnancy
Infertility
Treatment
Most patients with mild to moderate PID can be treated as an out patient
Some patients need hospital admission: Indications for admission are
Uncertain diagnosis
Pelvic abscess suspected
Pregnant patients
Co infection with HIV Internal Medicine

19

 As the infection is poly-microbial in nature instead of single, combination of antibiotics m should be

prescribed. The spectrum of activity of the antimicrobial agents should cover the following organisms:
N.gonorrhea, C. trachamatis, aerobic and anaerobic bacteria.
Antibiotics should be initiated empirically even before the microbiological report is available.
Recommended treatment for PID Out patient In patient
Ciprofloxacin 500 mg PO stat Or
Spectinomycin 2gm IM stat Plus Doxycycline 100 mg PO BID for 14 days Plus Metronidazole
500mg Po ID for 14 days
Admit the patient if there is no improvement within 72 hours
Metronidazole 500mg Po ID for 7 days Plus Clotrimazole vaginal tabs 200mg at bed time for 3 days
Non Specific: Adequate bed rest, analgesic,
If there are any obstetric or surgical complications, refer the patient as early as possible.
5. Inguinal bubo:
Inguinal bubo is an enlargement of the lymph glands in the groin area.
Etiology: The common sexually transmitted pathogen associated with Inguinal bubo include
o C.trachomatis serovar L1-L3 (Lymphogranuloma venereum or LGV)
o Haemophilus ducreyi (chancroid)
o Calymmatobacterium granulomatis (granuloma inguinale)
o Treponema pallidum (syphilis) may sometimes cause inguinal bubo Internal Medicine
Except in case of LGV, a bubo is rarely a sole manifestation of STD and is usually found together
with the etiologically related genital ulcer. Non-sexually transmitted local or systemic infections can
also cause inguinal lymphadenopathy.
Clinical feature:
Usually patients complain of unilateral or bilateral painful swelling in the groin, but buboes can be
painless.
It is important to ask for any history of associated genital ulcer.
Treatment:
Recommended treatment for Inguinal Bubo
Ciprofloxacin 500 mg PO BID for 3 days
PLUS
20

Doxycycline 100 mg PO BID for 14 days OR

Erythromycin 500 mg PO BQID for 14 days
Fluctuant buboes require aspiration through adjacent healthy skin (dont incise for drainage).
If genital ulcers are present, treat with the etiologically related cause of the ulcer.
6. Scrotal Swelling Syndrome
The cause of scrotal swelling depend on the age of the patient
For those younger than 35 years
N.gonorrhoeae
C.tracomatis
For those older than 35 years
Gram negative organisms
Tuberculosis
Other cause include : Brucellosis , Mumps , Onchocerciasis , Wuchereria
buncrofti
It is important to exclude other causes of scrotal swelling which may require urgent surgical evaluation
and management Internal Medicine
Testicular Torsion
Trauma
Incarcerated inguinal hernia
Complications of Scrotal Swelling: caused by STI include
Epididymitis
Infertility
Impotence
Prostatitis
Treatment of Scrotal swelling suspected of STI origin is similar to Urethral discharge.
Recommended treatment for Scrotal swelling
Ciprofloxacin 500 mg PO stat OR Spectinomycin 2gm IM stat

21

PLUS
Doxycycline 100 mg PO BID for 7 days OR Tetracycline 500 mg PO QID for 7 days
Supportive Treatment: Analgesia and scrotal support may be indicated if the patient has severe pain
Candidiasis
Definition
A mycosis usually confined to the superficial layers of skin or mucus membranes, presenting clinically
as oral thrush or vulvovaginitis.
Infectious agent
Candida albicans (most common cause)
Candida tropicalis (rare cause)
Communicable Disease Control
Epidemiology
Occurrence Worldwide. Candida albicans is often part of the normal human flora.
Reservoirs Humans
Mode of transmission contact with secretions or excretions of mouth, skin, vagina and feces, from
patients or carriers. Passage from mother to neonate during childbirth.
Incubation period variable.
Period of communicability - presumably while lesions are present.
Susceptibility and resistance Susceptibility is very low except in low host defense. It is common in
diabetes, HIVinfected; women are prone to vulvovaginitis in the third trimester of pregnancy. Oral
contraceptive users, individuals with prolonged steroid therapy are susceptible.
Clinical manifestation
Severe vulvar pruritis (prominent feature)
vaginal discharge (scanty, whitish, yellow, thick to form curds, non-offensive)
sore vulva due to itching
speculum examination thick whitish plugs attached to vaginal wall
vaginal epithlium bleeds when the plug is removed but the cervix is normal
Diagnosis
Based on clinical grounds
22

 Microscopic demonstration of pseudohyphae or yeast cells in infected tissue or body fluids (vaginal
discharge)
Culture (vaginal discharge)
Treatment
1. Nystatine vaginal pessary or
2. Miconazole or clotrmazele creams or
3. Keto conazole or
4. Fluconazele in recurrent cases
Prevention and control
1. Case treatment
2. Treatment of underlying medical conditions or predisposing factors
What is hepatitis?
Hepatitis means inflammation of the liver. The liver is a vital organ that processes nutrients, filters
the blood, and fights infections. When the liver is inflamed or damaged, its function can be affected.
Hepatitis is most often caused by a virus. In the United States, the most common types of viral
hepatitis are Hepatitis A, Hepatitis B, and Hepatitis C. Heavy alcohol use, toxins, some medications,
and certain medical conditions can also cause hepatitis.
What is Hepatitis B?
Hepatitis B is a contagious liver disease that results from infection with the Hepatitis B virus. When
first infected, a person can develop an acute infection, which can range in severity from a very mild
illness with few or no symptoms to a serious condition requiring hospitalization. Acute Hepatitis B
refers to the first 6 months after someone is exposed to the Hepatitis B virus. Some people are able to
fight the infection and clear the virus. For others, the infection remains and leads to a chronic, or
lifelong, illness. Chronic Hepatitis B refers to the illness that occurs when the Hepatitis B virus
remains in a persons body. Over time, the infection can cause serious health problems.
The best way to prevent Hepatitis B is to get vaccinated.
Acute hepatitis may occur as part of the clinical course of a number of viral infections, including
Human Cytomegalovirus, Epstein-Barr virus, Herpes Simplex Virus, Yellow Fever Virus and
Rubella. But the term "hepatitis virus" is usually used to describe infections caused by agents whose
primary tissue tropism is the liver. To date, at least five hepatitis viruses have been recognised and
these have been named, hepatitis A, B, C, D and E.
ClinicalFeatures
Hepatitis due to all these viruses presents clinically in a very similar fashion, especially during the
acute phase. Thus, a specific diagnosis can only be made in the laboratory. The majority of infections
23

are often asymptomatic or produce only mild non-specific symptoms. But, common clinical features
include: anorexia, nausea, vomiting, right upper quadrant pain and raised liver enzymes AST and
ALT. Jaundice is the hall mark of infection, but tends to develop late. Anicteric cases are also very
common.
ENTERICALLY TRANSMITTED HEPATITIS: A and E
Hepatitis A
Virology
Order: Picornavirales
Family: Picornaviridae
Genus: Hepatovirus
Species: Hepatitis A virus
Structure: small; 27 nm in diameter, non-enveloped spherical particle
Genome: +ssRNA (positive sense, single stranded RNA)

EM photo of Hepatitis A, courtesy of Prof Linda Stannard, UCT

Clinical Features
Incubation period 3-5 weeks (mean 28 days)
Incubation is followed by a pre-icteric phase lasting about 5 days.
The subsequent icteric phase resolved within 3 months in 85% of cases.
Convalescence may be prolonged, and fatigue and alcohol intolerance can last up to 18 months. There is
no chronic form of the disease.
Milder disease than Hepatitis B; asymptomatic infections are very common, especially in children.
Adults, especially pregnant women, may develop more severe disease. Complications:
Fulminant hepatitis: rare; 0.3-1.8 % of cases
Highest risk: pregnant women, elderly, pre-existing liver disease, other chronic medical conditions
Pathogenesis
Virus enters via the gut; replicates in the alimentary tract and spreads to infect the liver, where it
24

multiplies in hepatocytes. Viraemia is transient. Virus is excreted in the stools for two weeks preceding
the onset of symptoms.
Epidemiology
World-wide distribution; endemic in most countries. The incidence in first world countries is declining.
There is an especially high incidence in developing countries and rural areas, where 80-90% of people
are infected by the age of 5 years. The implication for South Africa is that most people, especially from
rural areas, are seropositive, and donated blood/plasma contains sufficient levels of antibodies for use
as passive immunity.
Transmission: Faecal-oral route
1. Case-to-case; via faecal-oral route. Virus is excreted in stool in large amounts before the onset
of symptoms. Outbreaks in creches are very common. In populations where oro-anal sex is
prevalent, HAV is sexually transmitted via the faecal-oral route.
2. Contamination of food or water with sewage
Infected food handlers
Shell fish grown in sewage-polluted water
Diagnosis
Virus cannot be cultured in vitro from clinical material; diagnosis depends on:
Serology HAV-specific IgM
Prevention
Active Immunization
Inactivated cell culture derived vaccine is available; it is recommended for travellers to third world
countries and, indeed, all adults who are not immune. It is the recommended form of post-exposure
prophylaxis if the exposure is identified early, and if there are no predisposing risk factors for severe
disease. If there are such risk factors, or if prophylaxis is delayed, passive immunization in addition to
vaccination is recommended.
Passive immunisation
Normal immunoglobulin (antibody prepared from pooled human serum) given to close contacts of acute
cases.
Protection is short lived: three months

25

Hepatitis E
Virology
Order: none
Family: Hepeviridae
Genus: Hepevirus
Species: Hepatitis E virus
Structure: 27-34 nm in diameter, non-enveloped spherical particle
Genome: +ssRNA (positive sense, single stranded RNA)
Clinical Features
Incubation period: 45 days [2-9 weeks]
Acute, self limiting hepatitis
Most cases occur in young adults, 15-40 years
Complications
10 % develop fulminant hepatitis (more common in pregnant women). Mortality rate is high (20-40 %).
Chronic hepatitis may develop in organ transplant patients and HIV-infected individuals and lead to
cirrhosis.
Pathogenesis
26

Acute hepatitis E is similar to hepatitis A; virus replicates in the gut initially, before invading the liver
and virus is shed in the stool prior to the onset of symptoms. Viraemia is transient. A large inoculum of
virus is needed to establish infection. Chronic hepatitis E infection seems similar to chronic hepatitis C
infections, but much about the pathogenesis is unknown.
Epidemiology
Prevalence of infection appears to be low in first world countries. Large outbreaks have been described
in India, Mexico and North Africa where the source of infection is usually gross faecal contamination
of drinking water supplies, which is the main source of infection.
Case-to-case transmission to household contacts appears to be uncommon. This suggests that a large
inoculum is needed to establish infection.
Various animal species such as the domestic pig have been identified as reservoirs of the virus and
outbreaks of human infections have been recorded associated with the consumption of inadequately
cooked meat.
Outbreaks of hepatitis E have been confirmed in South Africa, but the prevalence of infection is
unknown, as there are no routine laboratory tests yet available.
Diagnosis
No routine laboratory tests are available as yet in South Africa. Virus cannot be cultured in vitro.
1) Calicivirus-like particles in the stool, by electron microscopy
2) Specific IgM in serum (not yet available in South Africa)
3) PCR for HEV-specific sequences in stool or serum - currently research only
PARENTERALLY TRANSMITTED HEPATITIS B, C and D
Hepatitis B
Virology
Order: none
Family: Hepadnaviridae
Genus: Orthohepadnavirus
Species: Hepatitis B virus
Subtypes: A-H
Structure: 42 nm in diameter, enveloped spherical particle [also called the Dane particle]
Genome: circular DNA, incompletely double stranded; 3.2 kilobases in size
Excess surface antigen is produced, forming spheres and cylinders 22nm in diameter

27

EM photo of Hepatitis B, courtesy of Prof Linda Stannard, UCT

Clinical Features
Incubation period is long: 30-180 days, average 75 days
Insidious onset of symptoms. Tends to cause a more severe disease than Hepatitis A, but asymptomatic
infections occur frequently, especially in the very young, who tend to develop immunotolerance and
therefore a lesser immune response to the virus - this results in decreased inflammation in the liver as
well as a higher rate of chronicity. Approximately 5% of adults develop a chronic infection, whereas
90% of infants infected vertically go on to chronicity.
Pathogenesis
Infection is parenterally transmitted. The virus replicates in the liver and virus particles, as well as
excess viral surface protein, are shed in large amounts into the blood. Viraemia is prolonged and the
blood of infected individuals is highly infectious. The host immune response to the virus is responsible
for hepatocellular damage.
Complications

Persistant infection: Following acute infection, some individuals fail to eliminate the virus
completely and become persistantly infected. The likelihood of this happening varies with age of
exposure.
The virus persists in the hepatocytes and on going liver damage occurs because of the host's
immune response against the infected liver cells.
Chronic infection may take one of two forms:
o Chronic persistent hepatitis - the virus persists, but there is minimal liver damage
o Chronic active hepatitis - there is aggressive destruction of liver tissue and rapid
progression to cirrhosis or liver failure.
Patients who become persistently infected are also at risk of developing hepatocellular
carcinoma (HCC).
Fulminant hepatitis
28

This is a complication of acute infection. Rare; accounts for 1% of infections.

Extrahepatic manifestations include serum sickness, glomerulonephritis, and polyarteritis
nodosa, and are due to deposition of immune complexes.
Co-infection with HBV and HIV results in faster progression towards severe liver damage.

Epidemiology
Prevalence of disease in Africa
There are 400-500 million persistant carriers of Hepatitis B world wide, 50 million of whom are in
Africa. Carriage rates vary markedly in different areas. In South Africa, infection is much commoner
in rural communities than in the cities.
Hepatitis B is parenterally transmitted

Sexual intercourse Predominant mode of spread amongst adults

Close personal contact spread amongst children and in families, often called "horizontal"
spread. This is the most common mode of transmission in areas of high HBV prevalence, where
infection is acquired early in life. In South Africa, there is a high rate of infections in children
in the three to nine year age group. Also accounts for transmission in mental institutions and
children's homes.
Vertical transmission
Perinatal transmission from a carrier mother to her baby
Transplacental (rare)
During delivery
Post natal ?? breast feeding ?? close contact
This is a major mode of transmission in South East Asia.

Blood
Blood transfusions, serum products
Sharing of needles, razors
Tattooing, acupuncture
Renal dialysis
Organ donation
Note: these are rare today due to advances in screening blood and organ donors, and sterile
medical techniques.

Prevention
Active Immunization
Four types of vaccine are available
Serum derived - prepared from s Ag purified from the serum of HBV carriers
Recombinant sAg - made by genetic engineering in Saccharomyces cerevisiae, also known as Brewer's
yeast
Third generation vaccines genetically engineered producing different size surface antigens - these
29

vaccines are not available in South Africa

Combination vaccines - vaccines containing HBV vaccine in addition to vaccines against other
organisms, e.g. Hepatitis A+B
All these vaccines are equally safe and effective. Three doses induce protective levels of antibodies in
95% of vaccine recipients.
Universal immunization of infants was introduced in April 1995. Infants receive three doses: at 6, 10
and 14 weeks. However, if their mother is known to be chronically infected, they receive doses at birth,
1 month, and 6 months if their birth weight is >2kg, and an additional dose at 2 months if their birth
weight is <2kg.
In addition, vaccine should be administered to people at high risk of infection with HBV:

Health care workers

Sexual partners of chronic carriers
Infants of HBV carrier mothers
Post exposure prophylaxis

Passive Antibody
Both Hepatitis B immune globulin and vaccine should be administered to non immune individuals
following single episode exposure to HBV-infected blood.
Treatment of Chronic Hepatitis B infection
Two classes of drugs are used to treat chronic HBV infection
1. Interferons
Interferon 2a
Pegylated interferon 2a
Interferon- enhances the host immune response to HBV and improves immune control of the virus.
Clearance of infection (and immunity) is the best outcome, but is achieved in only around 25% cases
(after a six month course of treatment). Interferon is the best available treatment for chronic HBV,
but side effects and expense limit its use.
2. Nucleoside reverse transcriptase inhibitors
These drugs interfere with viral replication, but cannot clear HBV infection. They need to be taken
life long (as for HIV) to control infection..
Lamivudine (3TC, LAM)*
Tenofovir (TDF)*
Entecavir (ETV)
Adefovir (ADV)
Telbivudine (LdT)
Clevudine (CLV)
Emtracitabine (FTC)*
Note: * also used to treat HIV
not registered for use against HBV, but is similar to lamivudine

30

Viral antigens:
1) surface antigen (sAg) surface (envelope) protein of the dane particle
Secreted in excess into the blood as 22 nm spheres and tubules presence in serum indicates that virus
replication is occurring in the liver
2) e antigen (eAg) secreted protein; shed in small amounts into blood
presence in serum indicates that a high level of viral replication is occurring in the liver. May be
negative in carriers with mutations in the e antigen gene who nonetheless have high level viraemia.
3) core antigen (cAg) core protein present in infected liver cells, not found in blood
Antibody response:
1) Surface antibody (sAb, antiHBs)) becomes detectable late in convalescence following resolution of
infection, remains detectable for life; not found in chronic carriers; indicates immunity
2) e antibody (eAb, antiHBe) becomes detectable as viral replication falls
In a carrier, it indicates low infectivity
3) Core IgM rises early in infection
indicates recent infection
4) Core IgG Rises early
present for life in both chronic carriers as well as those who clear the infection
indicates exposure to HBV Usually tested as total core antibodies, and implies IgG in the absence of
IgM
HBV viral load:
HBV viral load measures level of HBV DNA in blood. This is the most reliable marker of infectivity.
It is more reliable than e antigen which can be negative in some carriers due to mutations in the e
antigen gene
Hepatitis B serology
(a) Acute, self limiting infection

31

(b) Chronic carrier state

Hepatitis C
The major cause of parenterally transmitted non A non B hepatitis. It eluded identification for many
years because the virus could not be cultured. In 1989, the viral genome was cloned and sequenced from
the serum of an infected chimpanzee. Much of the knowledge that we have today is based on analysis of
its genome sequence
32

Virology
Order: none
Family: Flaviviridae
Genus: Hepacivirus
Species: Hepatitis C virus
Structure: 55-65 nm in diameter, enveloped
Genome: +ssRNA (positive sense, single stranded RNA)
Genome has a high mutation rate
Viruses do not grow in cell culture, and only infect humans and chimpanzees
Clinical Features
The incubation period is 15-150 days. Most common presenting symptoms are fatigue and jaundice, but
60-70% of cases are asymptomatic. It is the cause of 15-20 % of acute hepatitis in the developed world.
Of note, 80% of newly infected individuals develop chronic infection..
Complications of chronic infection:

About 70% of those infected go on to develop a chronic infection.

Cirrhosis develops in 10-20% of chronic infections. Co-existence of other liver pathology
increases the severity of HCV induced liver disease.
Hepatocellular carcinoma (HCC) develops in 1-5% of HCV-infected people, and HCV is
responsible for about 25% of HCC cases.
Immune complex disorders common in HCV carriers
Co-infection with HIV is associated with more aggressive liver disease.
Extra-hepatic manifestations include unproven associations with cryoglobulinaemia, diabetes
mellitus, and B-cell lymphoma..

Epidemiology
Approximately 170 million people are infected world wide. The prevalence is high in parts of Africa,
the Eastern Mediterranean and South East Asia.
Transmission - similar to HBV
Intravenous drug abusers
Prior to the development of reliable labotatory tests for HCV, blood transfusions, blood products,
organ donations were important transmission events
Community acquired: mechanism unclear
Vertical transmission and sexual intercourse play a minor role
Increased infectivity in patients co-infected with HIV.
Diagnosis

33

1) Serology
HCV-specific IgG - indicates exposure, not infectivity; Useful for detecting chronic infections, but is
inadequate for detecting acute infection because it takes 2-3 months to become positive. .
2) PCR detects viral genome in patient's serum. The HCV genome is detectable in serum from 4-6
weeks post exposure (during acute infection). Indicates infectivity.
Treatment of Chronic infection: Interferon a in combination with Ribavirin results in clearance of
infection in up to 40% of cases. Pegylated interferon a is interferon that has had polyethylene glycol
attached to it. This increases the half life, which leads to fewer side effects due to a lower dose being
used.
There is no vaccine available
Hepatitis D Virus (delta agent)
In 1977 an novel protein was discovered in the serum of some patients who were infected with Hepatitis
B. It was named the delta antigen. Subsequent investigation showed that the protein was encoded by a
new virus, now called the hepatitis D virus (HDV).
It is a defective virus which requires Hepatitis B as a helper virus in order to replicate. Infection
therefore only occurs in patients who are already infected with Hepatitis B.
Clinial Features
Two forms of infection can occur - co-infection, where the person becomes infected with HDV and
HBV at the same time, and superinfection, where the person becomes infected with HDV after the
initial HBV infection. HDV leads to increased severity of liver disease in Hepatitis B carriers, and
the acute infection has an incubation period of about 35 days. Fulminant hepatitis is ten times more
common when a patient is co-infected with both viruses (HBV and HDV) simultaneously. With only
HBV, 20-30% go on to develop cirrhosis, while that figure rises to 70-80% with co-infection and
superinfection.

Treatment and prevention

No specific treatment is available. HDV infection may be controlled by preventing HBV surface
antigen production, but this may not always be possible even with complete suppression of HBV
replication.
HDV infection can be prevented by preventing infection with HBV, for which there is a successful
vaccine available.
Human retroviruses
Retroviruses infect a wide range of animal species and cause a variety of diseases including: tumours,
wasting and auto-immune diseases, immunodeficiency syndromes and aplastic and
34

haemolytic anaemias.
They are enveloped viruses with an RNA genome. The name is derived from the fact that the virus
particle contains an RNA dependent DNA Polymerase (Reverse transcriptase). This enzyme converts
the RNA genome into DNA, which then integrates into the host chromosomal DNA. The reverse
transcriptase is highly error prone and rapid genetic variation is a feature of this group of viruses.

Structure of the HIV virion. Taken from Wikipedia, redrawn by Carl Henderson, original by US
NIH.
The genus is divided into 5 sub genera.
Members of 2 of these genera cause disease in humans, namely Delta-retroviruses (HTLV 1 and 2) and
lentiviruses (HIV 1 and 2).
Genome organization
Retroviruses have a diploid genome (2 copies of RNA genome per virus particle). The genome codes for
at least three genes: gag, pol and env.
LTR - gag - pol - env - (onc) - LTR
LTR - Long terminal repeat - non coding regulatory sequences at each end of the genome, which are
necessary for integration into host chromosome and which also control gene expression
gag - codes for the core proteins, structural virion components
35

pol - reverse transcriptase (polymerase)

env - envelope glycoprotein
onc - oncogene
Oncogenes
Some retroviruses contain oncogenes. They are so called because their expression in virus-infected cells
is associated with tumour development. Retroviral oncogenes are derived from cellular genes picked up
during viral integration into host DNA, way back in evolution: Most oncogenes code for proteins with
growth promoting properties (such as growth factors, growth factor receptors or proteins that control
the cell cycle). Their expression can lead to uncontrolled proliferation of the infected cell. This may
contribute to tumour development. None of the retroviruses known to infect humans have oncogenes.
Defective virus
Many animal retroviruses are defective. Defective viruses are viruses that have lost a gene essential
for replication and can therefore only undergo productive infection if the cell that is harbouring the
virus is super-infected with a helper virus, which can supply the function of the lost gene.
Endogenous retroviral sequences
Integration into host DNA is a crucial step in the replication cycle of all retroviruses. This usually
occurs in somatic cells. However, during their co-evolution with vertebrates, some retroviruses
have integrated into germ cell DNA. This means that the retrovirus genome forms part of the genetic
material of every cell and is passed down from generation to generation. A staggering eleven percent of
the human genome is made up of these endogenous retroviral sequences. Fortunately they are all
defective and viral replication does not occur.

36

Life cycle of a typical retovirus

Human retroviruses
Six human retroviruses have so far been identified. All infect T cells.
HTLV 1 - T-cell leukaemias/lymphomas, Tropical spastic paraparesis
HTLV 2 - No known pathology
HIV 1 & 2 - AIDS
Two new human retroviruses were identified recently in a few individuals from Central Africa. They
are related to HTLV1 and 2 and have been called HTLV 3 and 4. No pathology has yet been attributed
to them.
HTLV 1
Epidemiology
HTLV1 has a world wide distribution, but there are hyperendemic foci in South West Japan,
the Caribbean and parts of West Africa. In high incidence areas, up to 30% of adults may be infected.
The sero-prevalence increases with age; infection is twice as common in females. Clustering of
infection in families is common. Spread occurs through blood transfusion and sexual intercourse as well
37

as mother to child transmission through breast feeding.

Clinical features
The vast majority of individuals infected by this virus harbour it asymptomatically and never develop
disease. However, they may develop one (or more) of the following complications:
1. T-cell leukaemia/lymphoma. Aggressive tumour of CD4 cells which infiltrates skin and brain.
Tumours are only produced after a prolonged latent period. Approximately 5% of HTLV 1 infected
individuals develop this malignancy. Malignant disease is more likely to occur in individuals who
acquire infection early in life.
1. HTLV1 associated myelopathy/Tropical spastic paraparesis. This is an aggressive nondemyelinating spastic paraparesis. Patients present with a gradual onset of symmetrical spastic
weakness, mainly affecting lower limbs. The lifetime risk of developing this disorder in
infected patients is approximately 2%. The risk is greater if infection is acquired in adulthood.
2. Infective dermatitis Chronic/Recurrent eczema of scalp, axillae, groin, ear, eyelids, para-nasal
skin and neck. Onset occurs in early childhood. Children who develop this condition have a
higher risk of acquiring T cell leukaemia or myelopathy later in life.
3. Uveitis
Laboratory Diagnosis
HTLV 1 specific 1gG antibody, ELISA and western blot
HTLV1 Proviral DNA in white blood cells detected by PCR
HTLV 2
This virus shares extensive nucleic acid sequence homology with HTLV 1. It was first isolated from a
patient with hairy cell leukaemia, but no specific pathology has yet been attributed to it.
HIV 1 and 2
Background
In the spring of 1981, a cluster of previously healthy homosexual men in New York and Los Angeles
were found to be suffering from severe immunodeficiency states associated with severe opportunistic
infections and rare malignancies. By 1982 the condition had been named the acquired immunodeficiency
syndrome (AIDS). It was realised by this time it had an infectious aetiology because the disease could
be transmitted by blood transfusions and blood products.
In 1983, a new retrovirus, termed lymphadenopathy associated virus (now called HIV 1) was isolated
from the T-cells of a patient with persistent generalised lymphadenopathy.
In 1986, a second closely related virus, termed HIV 2 was isolated from a patient from West Africa
38

with AIDS.
Currently (2010), about 34 million people are believed to be infected, world-wide; 22 million of these are
in sub-Saharan Africa. HIV 1 is the major cause of the AIDS pandemic; HIV 2 is of lower virulence
and infection has largely remained confined to West Africa.
Origin
AIDS is a new disease in humans. All the scientific evidence points to the disease having arisen in
Africa. The reason that we think this is that HIV is very closely related to viruses that infect African
monkeys, namely the simian immunodeficiency viruses (SIV). At least 10 crossings of the species
barrier from monkey to man have given rise to human infections with HIV strains.
Seven crossings gave rise to HIV2 strains; one gave rise to the HIV1 group M strains. (The HIV 1
group M strains account for the current pandemic.) Two further crossings have given rise to the HIV 1
group O and N strains, respectively (groups O and N are highly divergent stains of HIV 1 which have
only been found in a few individuals in the Cameroon). Another HIV 1 variant (group P) has reently
been described in an individual native to the Cameroon.
HIV 2 is most closely related to an SIV strain that infects Sooty Mangabey monkeys. The virus is
believed to have entered the human population in the 1940s. It is less infectious and causes a more
indolent disease than HIV 1. Infection has remained largely confined to West Africa.
HIV 1 strains are most closely related to SIV strains that infect chimpanzees. In the case of the group
M strains, the virus is thought to have entered the human population in the 1930s. Over the years it has
evolved in its new host and diversified, giving rise to the current pandemic.
The huge diversity of HIV 1 strains in the human population is due to the high mutation rate of the
virus. Strains can be grouped according to their genetic relatedness into subtypes. The different
subtypes have been named according to the letters of the alphabet (A to J).
Different subtypes predominate in different parts of the world. The subtype C strain of HIV 1 is the
commonest subtype to be found in sub-Saharan Africa.
Epidemiology - South Africa
HIV was introduced into South Africa in the 1980s. Since then the prevalence has increased
enormously. Since 1990, the growth of the epidemic has been monitored by an anonymous survey of
women attending ante-natal clinics in South Africa. The prevalence of HIV infection varies across the
country. It is lowest in the Western Cape and highest in KwaZulu/Natal. The overall prevalence of
HIV infection in adult South Africans in 2009 is estimated to be about 16.25 % (5.54 million people).
Transmission
Infection is transmitted in the same way as hepatitis B, but is much less infectious.
1.) Sexual intercourse:
This is the most common route of transmission world wide. The receptive partner is at greatest risk
There is an increased risk of transmission if partners have other sexually transmitted diseases and
39

during primary HIV infection.

2.) Vertical Transmission:
In the absence of ARV prophylaxis, 10-40% of HIV-exposed babies will acquire the infection from
their mothers. This is the second most common route of transmission world wide.
Infection may occur in utero
during birth (commonest)
post-natally, through breast feeding
3.) Exposure to blood:
Intra-venous drug abusers - sharing of needles
Needle-stick injuries - risk approximately 0.3% (depends on extent of the injury)
muco-cutaneous exposure - risk approximately 0.1%
Course of disease
HIV establishes a persistent infection in its host and only causes death many years later.
Primary infection
Most individuals experience a febrile illness about 2-4 weeks after exposure. This illness co-incides
with sero-conversion (development of antibodies) and so is often referred to as the sero-conversion
illness. The symptoms are similar to those of glandular fever, namely fever, sore throat, night sweats,
lymphadenopathy, diarrhoea. The illness is self limiting.
Asymptomatic phase
Following the primary infection, the patient enters a stage of clinical latency. During this time the
patient feels fine, but they are infectious as they have on-going viral replication. They also have HIV
antibodies in their blood (and will test positive in HIV tests). This healthy state may last many years.
Prodromal phase
As the CD4 counts drop, there is a gradual onset of a variety of prodromal disorders, such as weight
loss, fever, persistant lymphadenopathy, oral candidiasis and diarrhoea. These symptoms precede the
progression to AIDS.
Acquired Immunodeficiency Syndrome (AIDS)
Syndrome with the following features:
1) Constitutional disease: fever, diarrhoea, weight loss, skin rashes
2) Neuro-cognitave defects: dementia, myelopathy, peripheral neuropathy
3) Immunodeficiency: Increased susceptibility to opportunistic infections:
4) Rare malignancies: Kaposi sarcoma, oral hairy leukoplakia, lymphomas.
Pathogenesis
When a new infection is established, the first cells to be exposed are the dendritic cells. These cells are
40

resident in the skin and genital mucosa. It is their job to take up antigen in the tissues and to transport
it to regional lymph nodes where they present it to T cells. Dendritic cells express a receptor called DC
SIGN to which HIV can attach. HIV particles remain attached to the surface of the cell and are
passively transported to the very cells that HIV most likes to infect, namely CD4+ T cells. Cycles of
infection are set up in the CD4 cells in the lymphoid tissue.
Helper T cells are the primary target of HIV. They are cytokine secreting cells that provide the
signals to control the immune response. Without them the immune response cannot function
In the early days after infection, HIV is able to replicate to very high levels while the immune system
learns to deal with it. CD4 + levels in the blood fall and virus levels peak at approximately 21 days post
infection. The CD4 cell population in the gut is particularly severely affected early on. However, an
immune response to the virus does develop after a while and virus levels in the blood fall to a steady
state level. Unfortunately, the immune response is not able to control the infection completely and virus
replication continues in the lymphoid tissue. As time passes, the antiviral immunity begins to fail and
virus levels begin to rise again and the person succumbs to the infection.
Deterioration is linked to the loss of CD4+ cells:

Why do the T cells die?

1. Productive infection of the cell by the virus causes cell death with the release of new progeny virions.
2. Lysis of infected cells by the host's CTLs.
3. Apoptosis (activation induced cell death) of uninfected cells.
It is in the interests of the patient that the CTL killing of infected cells is efficient. If the immune
system can kill the infected cells before they release new progeny viruses, virus production is less
efficient and levels of virus are lower.
Thus patients with a strong CTL response have lower viral loads and survive for longer. Patients with
a weak CTL response have higher viral loads and survive for a shorter time.
Dying T cells are replaced by de novo synthesis of new T cells in the thymus or by cell division of
mature cells in the lymphoid organs. Only when the ability of the immune system to replace dead T
41

cells fails, do T cell numbers begin to fall.

Immune activation fuels disease progression. This is caused by ongoing virus replication and immune
attack in the lymphoid tissue which damages the delicate network of immune cells. The integrity of this
network is crucial for the immune system to function effectively. Once this starts to fail, cells receive
incorrect signals leading to:
Inappropriate activation and death (of un-infected cells) by apoptosis
Impairment of the function of the remaining cells
Failure to regenerate new cells
Immune activation is made worse by the fact that the lymphoid tissue of the gut is depleted early during
the clinical course of infection and the mucosal barrier to the entry of bacterial products from the gut is
compromised. These products can reach the systemic lymphoid organs such as lymph nodes and spleen
and induce local inflammatory responses.
Infection in infants
The source of infection is usually the mother. About one third of babies born to HIV positive mothers
will be infected unless antiretroviral prophylaxis is given to mother and baby. The most risky time for
transmission is during delivery, but in utero transmissions can also occur as well as post natal
transmission during breast feeding. Because of their immature immune responses, about half of the
infected infants do not have a phase of clinical latency, but instead develop a progressive illness and die
in the first year of life. The others will experience a latent period and may survive for 5-10 years or
longer. Symptoms of HIV infection in children include:
Failue to thrive, Lymphadenopathy, diarrhoeal disease, opportunistic infections, interstitial pneumonia,
parotitis etc. Tuberculosis, Pneumocystis jiroveci and CMV are very common opportunistic infections
that cause the death of HIV infected children in the first year of life. In South Africa HAART is
started as soon as the diagnosis is made in infants.
LABORATORY DIAGNOSIS and MONITORING
Serology
The mainstay of diagnosis is the detection of HIV specific antibody. IgG develops 4-6 weeks post
exposure and remains detectable for life. As all individuals become chronically infected, the presence of
HIV specific antibody indicates infection.
There are two situations where further tests may be necessary to confirm a diagnosis:
(a) Early infection - the period after exposure before antibody becomes detectable, (sometimes termed
the "window" period).
(b) Infants of HIV positive mothers: all have passively acquired HIV-specific antibody, but only 1040% are infected. This antibody may take 12 to 18 months to disappear.
In these instances, a more direct way of demonstrating the presence of HIV is necessary, namely the
detection of the virus itself:

42

Direct detection of virus

1. Viral p24 antigen in serum - This is a useful marker of early infection. It appears in the blood 3-5
weeks post exposure and becomes detectable approximately 6 days before antibody (during the so called
window period.) Once antibody appears, the p24 antigen is usually cleared.
Blood donors, source patients of needle-stick injuries and organ donors are routinely screened for both
p24 Antigen as well as HIV antibody. These days many laboratories (including our own) use a
combination HIV antibody/antigen test as the primary HIV screening test.
2. Detection of viral genome (proviral DNA or viral RNA) by PCR: This is a very sensitive indicator
of infection. PCR becomes positive about 2 weeks after infection and remains positive throughout the
course of the infection. This is the test of choice for confirming infection in infants of HIV positive
mothers
3. Culture of virus from peripheral blood mononuclear cells (PBMCs). This is difficult and not
routinely done.
Markers of disease progression:
These give an idea of the stage of infection and are also useful for monitoring response to antiviral
drugs:
CD4 count, total lymphocyte count
plasma viral RNA levels
DRUG THERAPY and PROPHYLAXIS
There is no cure for HIV. However, a number of anti-HIV drugs have been developed in recent years
that interfere with specific steps in the virus replication cycle. Used in combination, they halt viral
replication and can prolong the life of infected individuals. A regimen of at least three drugs
(HAART) has to be given simultaneously to suppress HIV replication. This is because drug resistance
develops very rapidly if they are used alone. Unfortunately these drugs need to be taken for life to
maintain viral suppression. They also have toxic side effects and response to therapy has to be carefully
monitored. Three classes of anti-retroviral drugs are used in South African public sector treatment
programmes:
Nucleoside and nucleotide reverse transriptase inhibitors
Non nucleoside reverse transcriptase inhibitors
Protease inhibitors
See lectures on antiretroviral therapy for more details.
PROPHYLAXIS
Short courses of anti-retroviral drugs have been used effectively to prevent HIV infection following
exposure:
Infants of HIV positive mothers: Various combinations of Antiretroviral drugs given to mother and
baby peri-partum, have been shown to reduce transmission to the baby.
43

Needle-stick injuries: The incidence of transmission is 0,3%; this can be reduced by 80% if AZT is
administered to the exposed person within 2 hours of exposure. Combinations of 2 or 3 different drugs
given for 28 days are routinely used in South Africa to prevent these transmissions.
Rape - Anti-retrovirals should be given to victim for 28 days. No human studies have been done to
prove their efficacy; but they have been shown to be effective in animal models.
VACCINE PROSPECTS
The development of an effective vaccine for HIV is probably still some years away. The difficulty is
that traditional approaches do not work. This is because the presence of HIV-specific antibody in the
blood does not prevent infection. There are various reasons for this:
1. There is extensive variability of the envelope antigens in the many subtypes of HIV that are
prevalent around the world.
2. Specific antibody may, in fact, enhance infection because antibody coated virus can bind to Fc
receptors on the surface of susceptible cells.
3. The envelope glycoprotein gp120 is heavily glycosylated and this masks the protein so that
antibodies can't bind to it.
4. 4. Critical epitopes on gp120 are hidden and are only exposed when the protein changes shape at
the time of fusion with the cell.
Nevertheless, research is on going to identify novel ways of presenting HIV antigens to the immune
system. To protect an individual from HIV, it is thought that a vaccine would need to generate a
potent specific cell mediated immune response at the site of entry of virus into the body, namely at
the mucosalsurfaces.
References:
1. National guideline for Syndromic aproch of Sexualy transmited infections, Federal MOH,
2005.
2. Kasper L., Braunwald E., Harrisons principles of Internal medicine, 16th Edition, Sexualy
transmited diseases, overview, pages 762-774 Internal Medicine

44

Other Important Infectious Diseases

1. Tetanus
Learning Objective: At the end of this unit the student will be able to
1. Define tetanus
2. Classify tetanus
3. Mention the etiology of tetanus
4. Describe the mode of transmission of tetanus
5. Explain the epidemiology of tetanus
6. Describe the pathophysiology of tetanus
7. Identify the clinical manifestations of tetanus
8. Describe the most commonly used method for the diagnosis of tetanus
9. Make a diagnosis of tetanus
10. Refer cases of tetanus to hospitals for better care and close follow up
11. Design appropriate methods of prevention for tetanus
Definitions
Tetanus is a neurologic disease characterized by increased muscle tone and spasms caused by toxin
released from the bacteria Clostridium tetani.
Etiologic Agent

Clostridium tetani is an anaerobic, motile Gram-positive rod that forms an oval, colorless, terminal
spore, which looks like a tennis racket or a drumstick. It is found worldwide in soil.

Spores may survive for years in soil. They are also resistant to different disinfectant and even to
boiling for less than 20 minutes.
Epidemiology
45

 Tetanus occurs sporadically and almost always affects non-immunized persons.

Partially immunized persons or fully immunized individuals who fail to maintain adequate immunity
are also affected.

Tetanus is more prevalent in developing countries like India, Bangladesh, Pakistan, eastern
Mediterranean, South America and Africa including Ethiopia.
Internal Medicine

Tetanus is more common in rural areas where there is frequent contact with soil. It also occurs more
frequently in warmer climates, during summer months and in males.
Neonates and young children are affected more in developing countries where immunization programs
are not comprehensive. Development of severe illness is seen more in the elderly. Most cases of tetanus
follow injuries especially during farming, gardening or other outdoor activities. Tetanus may also be
associated with surgery, otitis media, abortion or delivery.
Pathogenesis

Although C. tetani frequently contaminates wounds, germination and toxin production, however,
takes place in wounds with necrotic tissue, foreign bodies or infection that is active. Often the wound is
trivial or could seem to be healed from outside.

Tetanospasmin, a toxin produced by the bacteria in the wound binds to peripheral motor neuron
terminals, enters the axon and is taken to spinal cord and brainstem by retrograde transport. The toxin
then inhibits release of inhibitory neurotransmitter and - aminobutyric acid (GABA) with
diminished inhibition, there will be increased excitation spasm and rigidity. Tetanospasmin may also
block neurotransmitter release at the neuromuscular junction and produce weakness or paralysis.
Generalized tetanus occurs when toxin enters into blood stream and lymphatic to affect distant nerve
endings.
Clinical Manifestations

The incubation period (time between the injury and first symptom) of tetanus is about 7
10 days but it may range from 1 day to 2 months.

The period of onset (time between the first symptom and spasm) ranges 1 7 days.
The shorter the incubation period and period of onset, the more severe the disease becomes.
There are different forms of tetanus: neonatal, generalized and localized tetanus. The most common
form is generalized tetanus.
Generalized Tetanus

46

 The median time of onset after injury is seven days; but could occur as early as with in three days.
Usually the fist symptom is increased tone in the masseter muscle (trismus, or lockjaw) and patient is
unable to open his mouth.

Immediately after this the patient develops dysphagia, stiffness in the neck and back.
Then the patient develops contraction of facial muscles to produce rhesus sardonicus (sneer or
grimace).

There may be arched back (opisthotonos), generalized muscle spasm triggered by stimulus such as
light or noise.

Deep tendon reflexes may be exaggerated.

There may be dysphagia or paralytic ileus.
Localized tetanus: is a rare form of tetanus.

It presents with rigidity and spasm around the portal of entry.

While most localized tetanus have good prognosis, cephalic tetanus has high mortality. It comes after
head injury, injury to the face or ear infection.
Patients may come with wide ranges of wound severity, although most have trivial or healed wound. In
fact 15% 20 % of patients may not give history of injury.
Neonatal tetanus:

Occurs in neonates of non-immunized mother and those delivered in unhygienic condition.

It is a very severe form of tetanus with more than 90% mortality.
Neonates should be referred urgently to a near-by hospital if there is suspicion of clinical tetanus.
Tetanus may be graded according to severity. Grading is helpful in prognosis and management.

Grade I (mild) : moderate trismus, generalized spasticity

Grade II (moderate) : Moderate trismus, mild to moderate but short lasting spasms, tachypnea RR
30-35/min and mild dysphagia

Grade III (severe) : Severe trismus, generalized spasticity, prolonged spasms, respiratory
embarrassment RR >40/min, apnoeic spells, tachycardia >120/min and severe dysphagia

Grade IV (very severe) : Features of grade III plus severe autonomic disturbance of CVS. It
includes episodes of hypertension and tachycardia alternating with relative hypotension and
bradycardia or severe persistent hypertension (DBP >110 mmHg) or severe persistent hypotension
(SBP <90mmHg).
Poor prognostic factors in Tetanus:
47

 Patients with higher grades

Short incubation period and period of onset
Cephalic tetanus and
Patients with comorbidities have poor prognosis.
Diagnosis
The diagnosis of tetanus rests entirely on clinical grounds. But wounds should be cultured for C.tetani
or superinfection. CSF analysis is normal.
Treatment
The goals of treatment are

To eliminate source of toxin

Neutralize unbound toxin and
Prevent muscle spasm.
General measures:

Patients should be admitted to a quiet room in an ICU, where frequent monitoring is possible.
If there are wounds, they should be explored and cleaned.
Respiratory care: Intubation and tracheostomy may be required and should be done as early as
possible if indicated. These procedures are required for hypoventilation caused by laryngospasm or over
sedation or to avoid aspiration.

Autonomic dysfunction: No definitive treatment has so far been outlined. But hypotension requires
fluid expansion and vasopressor agents.

Other measures: hydration should be maintained. Naso-gastric tube can be inserted for nutrition.
Physiotherapy should be instituted as soon as possible to avoid contracture. Input and output should be
monitored. Bedsores and other infections should be prevented. Recovering patients should start active
immunization against ntetanus.
Specific Treatment;
Antibiotic treatment: This helps to eradicate the vegetative bacteria, not the toxin.

Crystalline penicillin 3 million units IV 6X a day for 10 days is used but metronidazole
500mg every 6 hrs or 1g every 12 hours can also be used. Erythromycin and
clindamycin are alternatives in patients allergic to penicillins.
48

Antitoxin: - This neutralizes only circulating toxins which are not bound.

Human tetanus immune globulin (TIG) is the choice and if available should be given early.
But tetanus antitoxin (TAT), which is available in our setup, can be given in doses of 10,000 IU
intravenous and 10,000 IU intra-muscular.
Control of muscle spasms:

Diazepam and Chlorpromazine are given 6 hourly, alternatively.

If spasms are not controlled by the above medication, neuromuscular blockers and mechanical
ventilation can be used.
2. Scabies
Scabies (from Latin: scabere, "to scratch"),[1] also known colloquially as the seven-year itch is a
contagious skin infection caused by the mite Sarcoptes scabiei.
The mite is a tiny, and usually not directly visible, parasite which burrows under the host's skin, which
in most people causes an intense itching sensation caused by an allergic response.
The infection in animals other than humans is caused by a different but related mite species, and is
called sarcoptic mange.
Scabies is classified by the World Health Organization as a water-related diseaseThe disease may be
transmitted from objects, but is most often transmitted by direct skin-to-skin contact, with a higher risk
with prolonged contact. Initial infections require four to six weeks to become symptomatic.
Reinfection, however, may manifest symptoms within as few as 24 hours. Because the symptoms
are allergic, their delay in onset is often mirrored by a significant delay in relief after the parasites
have been eradicated. Crusted scabies, formerly known as Norwegian scabies, is a more severe form of
the infection often associated with immunosuppression.
Scabies is one of the three most common skin disorders in children, along with tinea and pyoderma. As
of 2010 it affects approximately 100 million people (1.5% of the world population) and is equally common
in both sexes
Signs and symptoms
The characteristic symptoms of a scabies infection include intense itching and superficial burrows
The burrow tracks are often linear, to the point that a neat "line" of four or more closely placed and
equally developed mosquito-like "bites" is almost diagnostic of the disease.
Itching
In the classic scenario, the itch is made worse by warmth, and is usually experienced as being worse at
night, possibly because there are fewer distractions.[6] As a symptom, it is less common in the
elderly.[6]
49

Rash
Commonly involved sites of rashes of scabies
The superficial burrows of scabies usually occur in the area of the hands, feet, wrists, elbows, back,
buttocks, and external genitals
Except in infants and the immunosuppressed, infection generally does not occur in the skin of the face or
scalp.
The burrows are created by excavation of the adult mite in the epidermis.
In most people, the trails of the burrowing mites are linear or s-shaped tracks in the skin often
accompanied by rows of small, pimple-like mosquito or insect bites. These signs are often found in
crevices of the body, such as on the webs of fingers and toes, around the genital area, and under the
breasts of women.
Symptoms typically appear two to six weeks after infestation for individuals never before exposed to
scabies. For those having been previously exposed, the symptoms can appear within several days after
infestation. However, it is not unknown for symptoms to appear after several months or years
Acropustulosis, or blisters and pustules on the palms and soles of the feet, are characteristic symptoms
of scabies in infants
Crusted scabies
The elderly and people with an impaired immune system, such as HIV, cancer, or those
on immunosuppressive medications, are susceptible to crusted scabies (formerly called Norwegian
scabies). On those with weaker immune systems, the host becomes a more fertile breeding ground for
the mites, which spread over the host's body, except the face. Sufferers of crusted scabies exhibit scaly
rashes, slight itching, and thick crusts of skin that contain thousands of mites. Such areas make
eradication of mites particularly difficult, as the crusts protect the mites from topical miticides,
necessitating prolonged treatment of these areas.
Life cycle of scabies
In the 18th century, Italian biologist Diacinto Cestoni (16371718) described the mite now
called Sarcoptes scabiei, variety hominis, as thecause of scabies. Sarcoptes is a genus of skin parasites
and part of the larger family of mites collectively known as scab mites. These organisms have eight legs
as adults, and are placed in the same phylogenetic class (Arachnida) as spiders and ticks.
Sarcoptes scabiei mites are under 0.5 mm in size but are sometimes visible as pinpoints of white.
Pregnant females tunnel into the dead, outermost layer (stratum corneum) of a host's skin and
deposit eggs in the shallow burrows. The eggs hatch into larvae in three to ten days. These young mites
move about on the skin and molt into a "nymphal" stage, before maturing as adults, which live three to
four weeks in the host's skin. Males roam on top of the skin, occasionally burrowing into the skin. In
general, few mites usually occur on a healthy hygienic person infested with noncrusted scabies; about 11
females in burrows can be found on such a person

50

The movement of mites within and on the skin produces an intense itch, which has the characteristics of
a delayed cell-mediated inflammatory response to allergens. IgE antibodies are present in the serum and
the site of infection, which react to multiple protein allergens in the body of the mite. Some of these
cross-react to allergens from house-dust mites. Immediate antibody-mediated allergic
reactions (wheals) have been elicited in infected persons, but not in healthy persons;
immediate hypersensitivity of this type is thought to explain the observed far more rapid allergic skin
response to reinfection seen in persons having been previously infected (especially having been infected
within the previous year or two).
Because the host develops the symptoms as a reaction to the mites' presence over time, usually a fourto six-week incubation period after the onset of infestation is found. As noted, those previously infected
with scabies and cured may exhibit the symptoms of a new infection in a much shorter period, as little
as one to four days.
Scabies is contagious and can be spread by scratching an infected area, thereby picking up the mites
under the fingernails, or through physical contact with a scabies-infected person for a prolonged period
of time
Scabies is usually transmitted by direct skin-to-skin contact. It can also be spread through contact with
other objects, such as clothing, bedding, furniture, or surfaces with which a person infected with scabies
might have come in contact
Scabies mites can survive without a human host for 24 to 36 hours. As with lice, scabies can be
transmitted throughVsexual intercourse even if a latex condom is used, because it is transmitted from
skin-to-skin at sites other than sex organs
Pathophysiology
The symptoms are caused by an allergic reaction of the host's body to mite proteins, though exactly
which proteins remains a topic of study. The mite proteins are also present from the gut, in mite feces,
which are deposited under the skin. The allergic reaction is both of the delayed (cell-mediated) and
immediate (antibody-mediated) type, and involves IgE (antibodies, it is presumed, mediate the very
rapid symptoms on reinfection).
The allergy-type symptoms (itching) continue for some days, and even several weeks, after all mites
are killed. New lesions may appear for a few days after mites are eradicated. Nodular lesions from
scabies may continue to be symptomatic for weeks after the mites have been killed.
Diagnosis
Scabies may be diagnosed clinically in geographical areas where it is common when diffuse itching
presents along with either lesions in two typical spots or there is itchiness of another household member
The classical sign of scabies is the burrows made by the mites within the skin.
To detect the burrow, the suspected area is rubbed with ink from a fountain pen or a
topical tetracycline solution, which glows under a special light.

51

The skin is then wiped with an alcohol pad. If the person is infected with scabies, the characteristic
zigzag or Spattern of the burrow will appear across the skin; however, interpreting this test may be
difficult, as the burrows are scarce and may be obscured by scratch marks
A definitive diagnosis is made by finding either the scabies mites or their eggs and fecal
pellets. Searches for these signs involve either scraping a suspected area, mounting the sample
in potassium hydroxide and examining it under a microscope, or using dermoscopy to examine the skin
directly
Differential diagnosis
Symptoms of early scabies infestation mirror other skin diseases, including dermatitis, syphilis,
various urticaria-related syndromes, allergic reactions, and other ectoparasites such as lice and fleas
Prevention
Mass treatment programs that use topical permethrin or oral ivermectin have been effective in reducing
the prevalence of scabies in a number of populations.[4] No vaccine is available for scabies.
The simultaneous treatment of all close contacts is recommended, even if they show no symptoms of
infection (asymptomatic), to reduce rates of recurrence.
Since mites can survive for only two to three days without a host, objects in the environment pose little
risk of transmission except in the case of crusted scabies, thus cleaning is of little importance.
Rooms used by those with crusted scabies require thorough cleaning.
Management
A number of medications are effective in treating scabies; however, treatment must often involve the
entire household or community to prevent reinfection.
Options to control itchiness include antihistamines
Permethrin
Permethrin is the most effective treatment for scabies and is the treatment of choice. It is applied from
the neck down, usually before bedtime, and left on for about eight to 14 hours, then washed off in the
morning. One application is normally sufficient for mild infections. For moderate to severe cases,
another dose is typically applied seven to 14 days later Permethrin causes slight irritation of the skin,
but the sensation is tolerable.[6] The medication, however, is the most costly of topical treatments
Ivermectin
Ivermectin is an oral medication shown by many clinical studies to be effective in eradicating scabies,
often in a single dose It is the treatment of choice for crusted scabies, and is often used in combination
with a topical agent. It has not been tested on infants and is not recommended for children under six
years of age
Topical ivermectin preparations have been found to be effective for scabies in adults, and are attractive
due to their low cost, ease of preparation, and low toxicity.
52

It has also been useful for sarcoptic mange (the veterinary analog of human scabies).
Others
1) Other
treatments
include lindane, benzyl
benzoate, crotamiton, malathion,
and sulfur preparations.
2) Lindane is effective, but concerns over potential neurotoxicity has limited its availability in
many countries.
3) It is approved in the United States for use as a second-line treatment
4) Sulfur ointments or benzyl benzoate are often used in the developing world due to their low
cost;10% sulfur solutions have been shown to be effective and sulfur ointments are typically
used for at least a week
5) Crotamiton has been found to be less effective than permethrin in limited studies.]
6) Crotamiton or a sulfur preparation is often recommended instead of permethrin for children,
due to concerns over dermal absorption of permethrin

53

Prevention of Control of Zonotic Disease

1. Rabies
Learning Objective: At the end of this unit the student will be able to
1. Define rabies
2. Mention the etiology of rabies
3. Describe the mode of transmission of rabies
4. Explain the epidemiology of rabies
5. Describe the pathophysiology of rabies
6. Identify the clinical manifestations of rabies
7. Describe the most commonly used method for the diagnosis of rabies
8. Make a diagnosis of rabies
9. Refer people who were bitten by rabied animals to hospitals for post exposure prophylaxis
10. Design appropriate methods of prevention and control of rabies
Definition: Rabies in an acute central nervous system disease that is caused by rabies virus, an RNA
virus, which is transmitted by infected secretions.
Etiology: - The rabies virus is a single stranded RNA virus which belongs to the rhabdovirus family.
Epidemiology:
Rabies is found in animals in most regions of the world. Source of infection could be domestic or wild
animals.
Human infection occurs through contact with un-immunized domestic animals or exposure to wild
animals in the periphery. Humans are occasionally infected by wild animals like foxes and bats, but
domestic dogs are responsible for more than 90% of human cases worldwide.
The incubation period of rabies is very variable, which ranges from as early as 7 days to as late as
more than one year, but the mean incubation period is 1 to 2 months.
Pathogenesis: Rabies virus enters the body through skin or mucous membrane. There is initial
replication of virus at the muscles around port of entry. The virus then ascends to the CNS through the
neuromuscular junction. Once in the CNS, the virus replicates in the gray matters. The virus then
passes to other organs like kidneys, salivary glands, heart, and skin, following the autonomic nervous
system.
Passage of the virus into salivary gland facilitates further transmission.
Clinical manifestations:
Clinical manifestations can be divided into four stages.
a. Prodromal stage: usually it lasts less than 4 days; it is manifested by fever, headache,
malaise, and anorexia and vomiting.
b. Encephalitis phase: starts with excitation and agitation but later there will be
confusion, hallucination, aggressive behavior, muscle spasms, meningismus,

54

opisthotonus, seizure and focal paralysis. Patients may have fever, irregular pupils,
salivation, perspiration and postural hypotension.
c. Brainstem dysfunction: begins soon after the encephalitis phase. There will be multiple
cranial nerve deficits. Excessive salivation and inability to swallow results drooling of
saliva. Hydrophobia is seen in about 50% of cases.
d. Death: Patients rapidly develop coma and death is usually caused due to respiratory
failure (by apnea).
Laboratory Findings: Early in the course, routine investigations are normal. Later the white cell count
is usually moderately elevated, but it may as well be normal.
However, the diagnosis of rabies rests on identification of the virus or serologic tests.
Treatment
Once clinical disease appears, mortality is almost 100%. So far only 6 cases have recovered from
disease in the world. Therefore anyone with history of domestic or wild animal bite should be taken
seriously.
Post exposure prophylaxis: should be considered in people who had physical contact with saliva or
secretions of infected animals or bitten by unprovoked animal e.g. a dog may likely have rabies.
Post exposure prophylaxis of rabies includes:
a. Rigorous cleansing and treatment of the wound
b. Administration of rabies vaccine together with anti-rabies immunoglobulin.
c. As the incubation period of rabies is variable, post exposure prophylaxis should be
initiated as long as there is no clinical evidence of rabies.
Pre-exposure Prophylaxis: people who are at risk of contact with rabies like veterinarians, laboratory
workers and animal handlers should receive pre exposure prophylaxis.
3. Anthrax
Definition: anthrax is an infection that is caused by Bacillus anthracis. It mainly affects herbivorous
animals but humans are infected by contact with the causative agent from infected animals, by contact,
ingestion or inhalation.
Etiology: Bacillus anthracis is a large, aerobic, spore-forming, gram-positive rod, which is encapsulated
and non-motile.
Epidemiology: Anthrax is more common in herbivorous animals like cattle, sheep and goats.
They are infected while grazing on contaminated grass. Humans may acquire anthrax from
agricultural sites through contact with animals like butchering and feeding or industrial sites through
exposure to contaminated hides, wool or bones.
Pathogenesis:
A. Cutaneous anthrax is initiated when spores of B. anthracis are introduced through
abrasions of the skin or insect bite.
B. Inhalation anthrax is acquired by directly inhaling the agent to the alveoli.
C. Gastrointestinal form usually occurs after ingestion of raw or partially cooked meat
that is contaminated.
Anthracis goes to the blood stream and replicates rapidly. It is resistant to phagocytosis. It
also produces anthrax toxin, which causes edema and inhibition of polymorphonuclear
leucocyte function. Moreover, it causes release of cytokines, shock and death.
Clinical Manifestations
About 95% of anthrax is cutaneous form. 5% is inhalation, and that of gastrointestinal (GI) is very
rare. GI form is more common in areas where raw meat is ingested.
Cutaneous anthrax:
55

o The lesions are more common on exposed areas like face, neck and extremities.
o In the beginning, a small red macule develops within days. This will become popular
and pustular which then forms a central necrotic ulcer (black eshcar) with surrounding
edema; it is painless.
o Usually there is associated painful regional lymphadenopathy and fever is uncommon.
o Most patients recover spontaneously but about 10% develop progressive infection,
bacteremia, high grade fever and rapid death.
Inhalational anthrax (wool sorters disease):
This form resembles severe viral respiratory disease and thus diagnosis is difficult.
This form may be used as biological warfare.
Within 3 days of infection patients develop fever, dyspnea, stridor, hypoxemia, hypotension and may
die within 24 hours once patients become symptomatic.
Gastrointestinal anthrax: Patients may have nausea, vomiting, abdominal pain, bloody diarrhea, and
fever; they may develop ascites.
Treatment
Cutaneous anthrax
a. Can be treated with crystalline penicillin 2 million units 6 hourly until edema subsides
then oral penicillin for 7-10 days.
b. For allergic patients, ciprofloxacin, erythromycin, TTC or chloramphenicol may be
given.
c. Wound should be cleaned, debrided and dressed.
Inhalation or GI form
Should be treated with high dose penicillin 8-12 million units per day, divided into 4-6 doses.
Mortality rate
o Cutaneous Anthrax is 10-20%, for and almost.
o GI Anthrax can 50%
o Inhalational anthrax 100% for
Prevention:
Mass vaccination of animals
Avoiding feeding on infected cattle
Proper disposal of dead animals and
Keeping personal hygiene.

56

4. Brucellosis
Definition: Brucellosis is a zoonotic disease caused by Brucella species, which is characterized by
remittent type of fever and multi-organ involvement. It is transmitted to humans from infected
animals.
Etiology: It is caused by four different types of Brucella. They are small aerobic gram-negative bacilli;
they are non-motile and facultative intracellular parasites.
1) Brucella melitensis (the most common and most virulent type) acquired from goats, sheep and
camels.
2) Brucella abortus from cattle
3) Brucella suis from hogs
4) Brucela canis from dogs
Epidemiology:
It is found worldwide, but the true incidence is not known. In communities where brucellosis is
endemic, it occurs in children and family members of infected persons are at risk. Commonly affected
are farmers, meat-processing workers, veterinarians, and laboratory workers.
Brucella organism is transmitted commonly through the ingestion of untreated milk or milk products;
raw meat and bone marrow have been implicated. But it can also be transmitted by inhalation from
close contact with animals.
Pathogenesis: In the blood Brucella is ingested by polymorphonuclear leukocytes and macrophages but
they resist intracellular phagocytosis. Severity of the disease is largely determined by the outcome of
pathogen-phagocyte interaction. The organisms multiply, reach blood stream via lymphatics, and then
reside in different organs, the liver, spleen, bones, kidneys, lymph nodes, heart valves, nervous system
and testes. In infected organs there will be inflammatory responses or noncaseating granulomas. Serum
IgM will appear within a week and later IgG and IgA will develop.
Clinical manifestations and complications:
Brucellosis is a systemic illness and its manifestations mimic other febrile illnesses.
The incubation period is about 1-3 weeks. The illness may begin suddenly or it could be gradual.
The most common symptoms are fever, chills, diaphoresis, headache, myalgia, fatigue, anorexia, joint
and low back-pain, weight loss, constipation, sore throat and dry cough.
Patients may look well with no findings or may exhibit physical findings related to the organ affected.
Fever of brucellosis has no distinctive features but it occurs in late afternoons or evenings.
Patients may have reactive asymmetric polyarthritis involving larger joints; and lumbar vertebral
osteomyelitis.
Cardiovascular complications of Brucellosis include endocarditis, myocarditis, pericarditis,
thrombophlebites and pulmonary embolism.
Brucella can have respiratory manifestations like sore throat, tonsillitis, dry cough and even pneumonia
and lung abscess.
Gastrointestinal manifestations are generally mild and include nausea, vomiting, abdominal pain and
diarrhea; there is hepatosplenomegaly in about 15-20% of patients.

57

Patients may have genitourinary infection and present with epididymoorchitis, prostatitis, amenorrhea,
tubo-ovarian abscess, salphingitis, acute pyelonephritis and glomerulonephritis.
Nervous system involvement is uncommon but when involved patients may have meningitis,
meningoencephalitis, brain abscess, hemiplegia and cranial nerve deficit.
Other manifestations are conjunctivitis, retinopathy, skin involvement, abortion, anemia, leukopenia
and thrombocytopenia.
Diagnosis
The combination of history of exposure, clinical features and significantly raised levels of
Brucella agglutinin confirms the diagnosis of active brucellosis.
Treatment
The combination of doxycycline and aminoglycoside (gentamicin, or streptomycin) for 4 weeks followed
by the combination of doxycycline and rifampin for 4 to 8 weeks is the most effective treatment
modality.
Alternative regimen is combination of doxycycline and rifampin given for 8 to 12 weeks.
Patients with serious illness and complication need admission for treatment with intravenous
medications and possible surgical intervention.
Prevention - Immunization of animals, boiling or pasteurizing milk are important in preventing the
disease.

5. Toxoplasmosis
Definition
Toxoplasmosis is a systemic protozoal disease that can be either acute or chronic type with intracellular
parasite.
Toxoplasma gondii in which the parasite is responsible for the development of clinically evident disease,
including lymphadenopathy, myocarditis and encephalitis.
Infectious agent
Toxoplasma gondii
Epidemiology
Occurrence- Worldwide in mammals and birds. Infection in man is common. In the United States and
most European countries, the prevalence of sero-conversion increases with age and exposure. In Central
America, France, Turkey and Brazil, sero-prevalence is much higher, approaching 90% by age of 40.
Reservoir- The definitive hosts are cats and other felines, which acquire the infection mainly from
eating infected mammals (especially rodents) or birds and rarely from feces of infected cats. Only
felines harbor the parasite in the intestinal tract where the sexual stages of its life cycle takes place,
which result in the excretion of the oocyst in feces for 10-20 days or rarely longer. The intermediate
hosts of T. gondii include sheep, goats, rodents, cattle, chicken and birds.
Intermediate hosts are man and other animals.
The life cycle can be either hetroxenous (requiring two hosts) or monoxenous (one host). Both sexual
and asexual reproduction occurs in man.

58

There are five main developmental forms in the life cycle, but only trophozoites and cyst stages are
found in human. All stages occur in the felines (cats).
Toxoplasma has two forms
1. Tachyzoites- occur in the early acute stage of infection.
2. Bradyzoites-occur in the chronic stage of infection, develop slowly and multiply in the tissue to form
a true cyst.
Mood of Transmission
1. Ingestion of cysts in raw or under-cooked meat
2. Ingestion of oocysts in food, drink or from hands contaminated with feces of an infected cat.
3. Transplacental/congenital
4. Blood transfusion
5. Organ transplantation
Incubation period- from 10-23 days. One common source outbreak from ingestion of under-cooked meat
is possible.
Period of communicability- Not directly transmitted from person to person, except in utero. Oocysts
shed by cats sporulate and become infective 1-5 days later and may remain infective in water or moist
soil for about a year.
Cysts in the flesh of an infected animal remain infective as long as the meat is edible and uncooked.
Susceptibility and resistance- Susceptibility to infection is general, but immunity is readily acquired
and most infections are asymptomatic. Duration and degree of immunity are unknown, but are assumed
to be long-lasting or permanent.
Antibodies persist for a year, and probably for life. Patient undergoing cytotoxic or immunosuppressive therapy or patients with AIDS are at risk of developing the disease.
Clinical manifestation
General symptoms: Although severe symptoms may be noted, Toxoplasmosis gondii symptoms are mild
and mimic those seen in cases of infectious mononucleosis. The acute form of this disease is
characterized by fatigue, lymphodenitis, chills, fever, headache and myalgia. In addition to chronic
disease, the patient may develop maculopapular rash, encephalomyelitis and hepatitis; retinochoriditis
with subsequent blindness has been known to occur on rare occasions.
Congenital Toxoplasmosis: The typical symptoms in an infected child include hydrocephaly,
microcephaly, choreoretinitis, convulsion and psychomotor disturbance.
Most of these infections ultimately result in mental retardation, severe visual impairment or blindness.
Diagnosis
1) Clinical sign and symptom
2) Serological test
3) Demonstration of the agent in body fluid or tissue biopsy
4) cell culture
Treatment
1. Treatment is not routinely indicated for a healthy immunocompetent host, except in an initial
infection during pregnancy or the presence of active choreoretinitis and myocarditis or other organ
involvement.
2. The preferred treatment for those with severe symptomatic disease is: Pyrimethamine combined with
sufadiazine and folinic acid for four weeks.

59

3. For pregnant women, Spirmycin is commonly used to prevent placental infection. If ultrasound or
other studies indicate that fetal infection has occurred, Pyrimethamine and sulfadiazine should be
considered.
Treatment for infants
1. Pyrimethamine
2. Sufadiazine
3. Folinic acid
Prevention and control
1) The cause of primary infection with Toxoplasma can be reduced by avoiding eating under-cooked or
raw meat and avoiding cyst-contaminated materials (i.e. cats litter box).
2) Meat should be heated to 600c or frozen to kill cysts.
3) Hands should be washed thoroughly after work in the garden and all fruits and vegetables should be
washed.
4) Discourage cats from hunting.
5) Dispose cats feces daily.
6) Control stray cats and prevent them from gaining access
to sand boxes and sand piles.
7) Educate pregnant women.
a) To avoid cleaning litter pans or contact with cats.
b) Dietary meat; to heat to 60oc or freeze it.
c) To wear gloves during gardening.
8) Blood intended for transfusion into Toxoplasma seronegative immuno-compromised individuals
should be screened for antibody to toxoplasma gondii.
9) Patients with HIV/AIDS who have severe symptomatic toxoplasmosis should receive prophylactic
treatment (Prymethamine, sulfadizine, folinic acid) throughout their life span
5. Trichinosis
Trichinosis or trichiniasis, is a parasitic disease caused by eating raw or undercooked pork or wild
game infected with the larvae of a species of roundworm Trichinella spiralis, commonly called
the trichina worm. There are eight Trichinella species; five are encapsulated and three are not.
Only three Trichinella species are known to cause trichinosis: T. spiralis, T. nativa, and T. britovi.
Agent

The causative agents of trichinosis in humans include the three aforementioned species, however, T.
spiralis is the most clinically diagnosed cause of the disease due to its cosmopolitan distribution and
high pathogenicity.
Species and characteristics
a) T. spiralis is

most adapted to swine, most pathogenic in humans and is cosmopolitan in

distribution.
b) T. britovi is the second most common species to infect humans; it is distributed throughout
Europe, Asia, and northern and western Africa usually in wild boar and domesticated pigs.
c) T. nativa, which has a high resistance to freezing, is found in the Arctic and subarctic regions;
reservoir hosts include polar bears, arctic foxes, walruses and other wild game.

60

d)
e)
f)
g)
h)

T. pseudospiralis infects birds and mammals, and has demonstrated infection in humans; [5] it is
a nonencapsulated species.
T. papuae infects both mammals and reptiles, including crocodiles, humans, and pigs; this
species, found in Papua New Guinea and Thailand, is also nonencapsulated.
T. nelsoni, found in eastern Africa, has been documented to cause a few human cases.
T. murrelli also infects humans, especially from black bear meat; it is distributed among wild
carnivores in North America.
T. zimbabwensis can infect mammals and possibly humans; this nonencapsulated species was
detected in reptiles of Africa.

Life cycle
1) The typical life cycle for T. spiralis involves humans, pigs, and rodents. Pigs become infected
when they eat infectious cysts in raw meat, often pork or rats (sylvatic cycle).
2) Humans become infected when they eat raw or undercooked infected pork (domestic cycle).
After humans ingest the cysts from infected undercooked meat, pepsin and hydrochloric acid
help free the larvae in the cysts in the stomach.
3) The larvae then migrate to the small intestine, where they molt four times before becoming
adults.
4) Thirty to 34 hours after the cysts were originally ingested; the adults mate, and within five
days produce larvae.
5) The worms can only reproduce for a limited time because the immune system will eventually
expel them from the small intestine. The larvae then use their piercing mouthpart, called the
"stylet", to pass through the intestinal mucosa and enter the lymphatic vessels, and then enter
the bloodstream
6) The larvae travel by capillaries to various organs, such as the retina, myocardium, or lymph
nodes; however, only larvae that migrate to skeletal muscle cells survive and encyst.
7) The larval host cell becomes a nurse cell in which the larvae will be encapsulated. The
development of a capillary network around the nurse cell completes encystation of the larvae.

61

Diagnosis
Diagnosis of trichinosis is confirmed by a combination of exposure history, clinical diagnosis, and
laboratory testing.
Exposure history

An epidemiological investigation can be done to determine a patient's exposure to raw infected meat.
Often, an infection arises from home-preparation of contaminated meat, in which case microscopy can
be used to determine the infection. However, exposure does not have to be directly from an infected
animal. Other exposure includes the consumption of products from a laboratory-confirmed infected
animal or by sharing a common exposure as a laboratory-confirmed infected human.
Clinical diagnosis

Clinical presentation of the common trichinosis symptoms may also suggest infection. These symptoms
include circumorbital edema, splinter hemorrhage, nonspecificgastroenteritis, and muscle pain.
The case definition for trichinosis at the European Center for Disease Control states "at least three of
the following six: fever, muscle soreness and pain, gastrointestinal symptoms, facial
edema, eosinophilia, and subconjuctival, subungual, and retinal hemorrhages."
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Laboratory testing

Blood tests and microscopy can be used to aid in the diagnosis of trichinosis. Blood tests include a
complete blood count for eosinophilia, creatine phosphokinase activity, and various immunoassays
such as ELISA for larval antigens.
Treatment and vaccines

As is desirable with most diseases, early treatment is better and decreases the risk of developing
disease. If larvae do encyst in skeletal muscle cells, they can remain infectious for months to years.
Primary treatment

Early administration of anthelmintics, such as mebendazole or albendazole, decreases the likelihood

of larval encystation, particularly if given within three days of infection.[12]However, most cases are
diagnosed after this time.
Mebendazole (200400 mg three times a day for three days) or albendazole (400 mg twice a day for
814 days) are given to treat trichinosis.
These drugs prevent newly hatched larvae from developing, but should not be given to pregnant women
or children under two years of age.
Secondary treatment

After infection, steroids, such as prednisone may be used to relieve muscle pain associated with larval
migration.
Vaccine research

There are currently no vaccines for trichinosis, although experimental mice studies have suggested a
possibility. In one study, microwaved Trichinella larvae were used to immunize mice, which were
subsequently infected. Depending on dosage and the frequency of immunization, results ranged from a
decreased larval count to complete protection from trichinosis.
Another study, Dea-Ayuela et al. (2006) used extracts and excretory-secretory products from first
stage larvae to produce an oral vaccine.[17] To prevent the gastric acids from dissolving the antigens
before reaching the small intestine, scientists encapsulated the antigens in a microcapsule made of
copolymers. This vaccine significantly increased CD4+ cells and increased antigen-specific serum IgGq
and IgA, resulting in a statistically significant reduction in the average number of adult worms in the
small intestine of mice. The significance of this approach is that if the white blood cells in the small
intestine have been exposed to Trichinella antigens (through vaccination) then, when an individual gets
infected, the immune system will respond to expel the worms from the small intestine fast enough to
prevent the female worms from releasing their larvae. Yuan Gu et al. (2008) tested a DNA vaccine on
mice which "induced a muscle larvae burden reduction in BALB/c mice by 29% in response to T.
spiralis infection".[18] Researchers trying to develop a vaccine for Trichinella have tried to using
either "larval extracts, excretory-secretory antigen, DNA vaccine, or recombinant antigen protein."
Prevention
Legislation

Laws and rules required of food producers may improve food safety for consumers, such as the rules
established by the European Commission for inspections, rodent control, and improved hygiene.
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Education and training

Public education about the dangers of consuming raw and undercooked meat, especially pork, may
reduce infection rates. Hunters are also an at-risk population due to their contact and consumption of
wild game, including bear. As such, many states, such as New York, require the completion of a course
in such matters before a hunting license can be obtained
Food preparation

Larvae may be killed by the heating or irradiation of raw meat. Freezing is only usually effective
for T. spiralis, since other species, such as T. nativa, are freeze resistant and can survive long-term
freezing.

All meat (including pork) can be safely prepared by cooking to an internal temperature of
165F (74C) or more for 15 seconds or more.

Wild game: Wild game meat must be cooked thoroughly (see meat preparation above) Freezing
wild game does not kill all trichinosis larval worms. This is because the worm species that typically
infests wild game can resist freezing.

Pork: Freezing cuts of pork less than 6 inches thick for 20 days at 5 F (15 C) or three days at

4 F (20 C) kills T. spiralis larval worms; but this will not kill other trichinosis larval worm
species, such as T. nativa, if they have infested the pork food supply (which is unlikely).
Hygienic pig farming

Keeping pigs in clean pens with floors that can be washed (such as concrete)
Not allowing hogs to eat carcasses of other animals, including rats, which may be infected
with Trichinella
Cleaning meat grinders thoroughly when preparing ground meats
Control and destruction of meat containing trichinae, e.g., removal and proper disposal of porcine
diaphragms prior to public sale of meat

64