Microbiology and Health – Reproductive Tract Infections

1. Introduction to the anatomy

The male genital anatomy is quite simple. The gonads are the testicles,
enclosed in an outer pouch called the scrotum. The testicles produce
hormones and sperm. Sperm is carried by the vas deferens to the urethra.
They are released during ejaculation with the seminal fluid. The seminal
fluid is produced by the prostate gland to a large extent. The penis is an
erectile organ that allows copulation, sperm ejection, and urine evacuation,
since the urethra is both part of the urinary and reproductive tract. At the
end of the penis there is the glans. Reproductive tract infections can, then,
be worsened, if the pathogen travels up the urethra and becomes
responsible for a urinary tract infection.
In women, the gonads are the ovaries. They produce eggs and hormones.
The egg is ejected during ovulation into the fallopian tube. This tube
connects the ovaries to the uterus. The uterus is a hollow organ that will
house the embryo during pregnancy. The vagina is a flexible canal that
connects the uterus to the vulva. The vulva is the outer part of the female
reproductive tract. It consists of the labia and the clitoris. It is worthy of
note that the proximity between the vagina and the anus in the female
anatomy can be a big factor regarding vaginal infections, since enteric
pathogens present in the gut are expelled during defecation and can easily
reach the vaginal opening.

2. Location of infection
Reproductive tract infections can be localized anywhere within the
anatomy, with the vagina, vulva, penis, scrotum, cervix and anus being the
most frequent spots. Some reproductive tract infections can also spread to
the mouth and eyes, through specific sexual acts.
In the female anatomy, RTI’s can be characterized as upper RTI’s (if they
occur in the endocervix, uterus or the ovaries) or as lower RTI’s (if they
take place in the ectocervix, vagina or vulva). This distinction isn’t made
often in men.
 3. Symptoms and signs associated
The symptoms of a reproductive tract infection differ from men to women,
due to their anatomy. In men, it is common to observe the following set of
symptoms:
 Burning or itching sensation in the penis
 Discharge under the foreskin
 Pain around the pelvis
 Sores, bumbs or blisters in the penis or scrotum
 Pain while urinating
 Bleeding from the penis
 Frequent or painful urination
 Foul smell
 Penile swelling
In women, on the other hand, the signs listed below are often indicative of
a genital tract infection:
 Burning or itching sensation in the vagina
 Change in the consistency and color of vaginal discharge
 Uncommon vaginal odor
 Pain around the pelvis
 Sores, bumbs or blisters in the vulva
 Pain while urinating and during penetrative intercourse
 Frequent urination
 Unusual bleeding from the vagina
Any of these symptoms should prompt a doctor visit to assess the potential
underlying health problems.
https://www.medicalnewstoday.com/articles/penis-infections
https://www.healthline.com/health/vaginal-infection
 4. Etiology of infection
 Host-related causes:
 Host’s immunity response to infection
 Hormonal equilibrium – sex hormones like estrogen and
progesterone influence the composition of the vaginal
microbiome, which is intrinsically linked to RTIs and their
effect on the body. [1]
 Systemic allergic response
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936955/

 Pathogen-related causes:
 Virulence factors
 Pathogenesis
 Presence of capsule or other protective structures
https://www-amboss-com.emedien.ub.uni-
muenchen.de/de/wissen/Entz%C3%BCndungen_des_weiblichen_Genitaltr
akts/

5. Microorganisms selected
 Candida albicans
 Route of transmission: Candida albicans is transmitted by
direct or indirect contact with contaminated people or objects.
http://hygiene-in-practice.com/pathogen/candida-albicans-en/
 Conditions that facilitate infection: If a patient’s immune
system is weakened after surgery or chemotherapy, for
example as a result of a disease, Candida becomes a pathogen.
In addition, therapy with an antibiotic can lead to the
destruction of the skin flora, and facilitate the penetration of
the fungus. http://hygiene-in-practice.com/pathogen/candida-
albicans-en/
 Symptoms: Vaginal itching or soreness, pain during sexual
intercourse or when urinating, and abnormal vaginal
discharge. Vaginal candidiasis is often mild. However, some
women can develop severe infections involving redness,
swelling, and cracks in the wall of the vagina.
 https://www.cdc.gov/fungal/diseases/candidiasis/genital/index.
html
 Diagnosis + specimen collection: usually is diagnosed by
blood sample or swab, followed by a PCR or selective culture.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5925725/
 Treatment: amphotericin B, echinocandin, or fluconazole for
systemic infections, nystatin for oral and esophageal
infections, and clotrimazole for skin and genital yeast
infection. https://doi.org/10.3109/13693786.2011.583943

 Neisseria gonorrhoeae
 Route of transmission: N. gonorrhoeae is transmitted through
vaginal, oral, or anal sex. It can also be transmitted to the
newborn during passage through the birth canal if the mother
has untreated genitourinary infection.
https://www.cdc.gov/std/gonorrhea/stdfact-gonorrhea-
detailed.htm
 Conditions that facilitate infection: unprotected sexual contact.
 Symptoms: Many men with gonorrhea are asymptomatic.
When present, signs and symptoms of urethral infection in
men include dysuria or a white, yellow, or green urethral
discharge that usually appears one to fourteen days after
infection. In cases where urethral infection is complicated by
epididymitis, men with gonorrhea may also complain of
testicular or scrotal pain. Most women with gonorrhea are
asymptomatic. Even when a woman has symptoms, they are
often so mild and nonspecific that they are mistaken for a
bladder or vaginal infection. The initial symptoms and signs in
women include dysuria, increased vaginal discharge, or
vaginal bleeding between periods. Women with gonorrhea are
at risk of developing serious complications from the infection,
regardless of the presence or severity of symptoms.
https://www.cdc.gov/std/gonorrhea/stdfact-gonorrhea-
detailed.htm
 Diagnosis + specimen collection: Swabs taken from the
urethra, cervix, pharynx, rectum or other site should be rolled
onto a slide first and then sent to the laboratory in an
appropriate transport medium. In the lab, Gram stain can be
performed on discharges smeared on the slide, c ulture on both
 selective and nonselective media should be used (culture of N.
gonorrhoeae provides definitive diagnosis, and isolates
provide valuable information on patterns of antibiotic
resistance and other epidemiological markers) and nucleic acid
testing can be performed on cervical and urethral swabs, and
urine. In women, polymerase chain reaction (PCR) testing of
urine is less sensitive than PCR testing of endocervical swab
specimens. https://www.health.vic.gov.au/infectious-
diseases/gonorrhoea
 Treatment: The current treatment recommended by the CDC is
an injected single dose of ceftriaxone, however there are many
N. gonorrhoeae antibiotic resistant strains which do not
currently have a cure.
https://www.cdc.gov/std/gonorrhea/stdfact-gonorrhea-
detailed.htm

 Treponema pallidum
 Route of transmission: You can get syphilis by direct contact
with a syphilis sore during vaginal, anal, or oral sex. Syphilis
can spread from a mother with syphilis to her unborn baby.
You cannot get syphilis through casual contact with objects.
https://www.cdc.gov/std/syphilis/stdfact-syphilis.htm
 Conditions that facilitate infection: unprotected sexual contact.
 Symptoms: There are four stages of syphilis (primary,
secondary, latent, and tertiary). Each stage has different signs
and symptoms. During the first (primary) stage of syphilis,
you may notice a single sore or multiple sores. The sore is the
location where syphilis entered your body (usually, penis and
vagina). During the secondary stage, you may have non-itchy
rough, red or brown skin rashes, fever, swollen lymph nodes,
sore throat, hair loss, headaches, weight loss, muscle aches
and fatigue. The latent stage of syphilis is a period when there
are no visible signs or symptoms. Without treatment, you can
continue to have syphilis in your body for years. Most people
with untreated syphilis do not develop tertiary syphilis.
However, when it does happen, it can affect many different
organ systems. These include the heart and blood vessels, and
the brain and nervous system, resulting in death.
https://www.cdc.gov/std/syphilis/stdfact-syphilis.htm
  Diagnosis + specimen collection: Treponema pallidum, cannot
be cultured, and there is no single optimal alternative test.
Serological testing is the most frequently used approach in the
laboratory diagnosis of syphilis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095002/
 Treatment: A single injection of long-acting Benzathine
penicillin G can cure the early stages of syphilis. This includes
primary, secondary, or early latent syphilis. CDC recommends
three doses of long-acting Benzathine penicillin G at weekly
intervals for late latent syphilis or latent syphilis of unknown
duration. https://www.cdc.gov/std/syphilis/treatment.htm

 Trichomonas vaginalis
 Route of transmission: Sexually active people can get trich by
having sex without a condom with a partner who has trich. In
women, the infection is most commonly found in the lower
genital tract (vulva, vagina, cervix, or urethra). In men, the
infection is most commonly found inside the penis (urethra).
https://www.cdc.gov/std/trichomonas/stdfact-
trichomoniasis.htm
 Conditions that facilitate infection: unprotected sexual contact.
 Symptoms: Men with trich may notice itching or irritation
inside the penis, burning after peeing or ejaculating, and
discharge from the penis. Women with trich may notice
itching, burning, redness or soreness of the genitals,
discomfort when peeing, and a clear, white, yellowish, or
greenish vaginal discharge (i.e., thin discharge or increased
volume) with a fishy smell.
https://www.cdc.gov/std/trichomonas/stdfact-
trichomoniasis.htm
 Diagnosis + specimen collection: diagnosis can be done
through a sample of vaginal fluid for women or a swab from
inside the penis (urethra) for men observed under a
microscope. If the parasite can be seen under the microscope,
no further tests are needed. If the test doesn't show the
parasite, but your provider thinks you may have
trichomoniasis, other tests such as rapid antigen test and
nucleic acid amplification test may be done.
 https://www.mayoclinic.org/diseases-
conditions/trichomoniasis/diagnosis-treatment/drc-20378613
 Treatment: Treatment of trichomoniasis requires an oral
antibiotic that is effective against infections caused by this
parasite. Treatment can be given during pregnancy. Options
may include a megadose (one large dose) of either
metronidazole (Flagyl), tinidazole (Tindamax) or secnidazole
(Solosec) or multiple doses of metronidazole or tinidazole.
https://www.mayoclinic.org/diseases-
conditions/trichomoniasis/diagnosis-treatment/drc-20378613

 Herpes simplex virus 1

 Route of transmission: HSV-1 is transmitted by contact with
an infected person who has reactivations of the virus. It can
also be transmitted vertically during childbirth.
https://www.who.int/news-room/fact-sheets/detail/herpes-
simplex-virus
 Conditions that facilitate infection: Unprotected sexual
contact.
 Symptoms: Both oral and genital herpes are mostly
asymptomatic or unrecognized but can cause painful blisters
or ulcers at the site of infection, ranging from mild to severe.
Additionally, symptoms of a new infection often include fever,
body aches and swollen lymph nodes. Infection is lifelong,
and symptoms can recur over many years. Genital herpes
caused by HSV-1 typically does not recur frequently.
https://www.who.int/news-room/fact-sheets/detail/herpes-
simplex-virus
 Diagnosis + specimen collection: Often, the appearance of
herpes simplex virus is typical and no testing is needed to
confirm the diagnosis. If a health care provider is uncertain,
herpes simplex can be diagnosed with lab tests, including
DNA -- or PCR -- tests and virus cultures.
https://www.webmd.com/genital-herpes/pain-management-
herpes#1
 Treatment: Some medications are available to reduce the
severity and frequency of symptoms, but they cannot cure the
infection. https://www.who.int/news-room/fact-
sheets/detail/herpes-simplex-virus
 6. Routes of transmission
Not all reproductive tract infections are transmissible, such as some yeast
infections. However, most RTIs are transmitted from one person to another
through contact with infected body fluids, including blood, semen, vaginal
discharge, etc.
However, there exist other ways RTIs can be transmitted through, such as
needle reuse, blood transfusion, touching someone that is infected, and
even from mother to baby while pregnant or during labor.
https://www.invitra.com/en/sexually-transmitted-diseases/

7. Epidemiology
When it comes to RTIs, most research is directed towards STIs which
assume the following numbers.

 +1 Million STIs are acquired daily worldwide. [1]

 Four main STIs Infections by number of new cases (2020):
Chlamydia (129M Infected), Gonorrhea (82M Infected), Syphilis
(7.1M Infected) and Trichomoniasis (156M Infected). [1]
In industrialized countries, there was a decline in STI numbers during the
Second World War, which was then maintained low by more extensive
sexual education and the advancement of medicine. Recently, bacterial
RTIs are less common than viral ones, such as HPV and HIV. [3]
In developing countries, STIs remain major health problems. Infection rates
are similar in both women and men, but women and infants bear the major
burden of complications and serious sequelae. [3]

[1]: https://www.who.int/news-room/fact-sheets/detail/sexually-
transmitted-infections-(stis)
[3]: De Schryver A, Meheus A. Epidemiology of sexually transmitted
diseases: the global picture. Bull World Health Organ. 1990;68(5):639-54.
PMID: 2289300; PMCID: PMC2393188.
[4]: Van Gerwen, O.T., Muzny, C.A. & Marrazzo, J.M. Sexually
transmitted infections and female reproductive health. Nat Microbiol 7,
1116–1126 (2022). https://doi.org/10.1038/s41564-022-01177-x
When it comes to non-sexually transmitted RTIs, a study conducted in
Senegal with 276 symptomatic maternity patients showed that they were
very prevalent. In fact, 69,6% of these patients (192 of 276) had an RTI,
the most common vaginal infections being bacterial vaginosis (39.5%) and
vaginal candidiasis (29%).
https://www.researchgate.net/figure/Aetiology-and-prevalence-of-lower-
genital-tract-infections-among-symptomatic-women-of_tbl2_333511069

8. Conditions that facilitate host infection

There are several risk factors that increase the likelihood of an individual
contracting a genital tract infection. Some of these include:
• Unprotected sexual contact – intercourse should always include a
physical barrier like a female or male condom, especially if it occurs
with a lot of different partners whom have not been previously tested
for STI’s. The condom should always be changed when engaging in
different acts (such as when changing from anal to vaginal sex).
Penetrative sexual activity can also lead to a disregulation of the
vaginal microbiota and result in yeast infections.
• Poor genital hygiene – this includes cleaning the genitals
appropriately and frequently with water and mild soap, and having a
correct wiping technique after using the bathroom (always from the
front to the back). Like previously mentioned, the vagina and the
anus are in very close proximity and enteric microorganisms can
easily travel between them.
• Misuse of vaginal cleaning products – the vagina is a self-cleaning
organ and should not come into contact with any external products,
at the risk of disrupting the vaginal microbiota. Despite there being
many products marketed for this purpose, one should always clear
with a gynecologist before utilizing soaps or other cleaning products
inside the vaginal opening.
• Pregnancy – e.g., candidiasis tends to occur during pregnancy
because of changes in the immune system, increased production of
glycogen, and higher estrogen levels.
 • Use of irritant lubricants – lubricant products used during sex should
be body safe (allergen free) and water based so they don’t degrade
the condoms.
• Unregulated use of antibiotics – antibiotics kill both the bad
microorganisms in your body and the natural microbiota. This
includes the fungi and bacteria that maintain vaginal balance. If any
of these are erradicated, the vaginal microbiota will suffer
deregulation.
• Hormonal changes
• Use of IUD or spermicide as birth control
• Not wearing appropriate underwear – underwear should be made of
cotton (or a breathable, natural fabric) and sized correctly to ensure
air flow to the genitals.
• Prolonged use of sanitary products – period products like pads and
tampons should be changed frequently to impede fungi
overproduction that can lead to yeast infections.

https://www.medicalnewstoday.com/articles/vaginal-infections#prevention
https://www.medicalnewstoday.com/articles/322210

9. Diagnosis/ product examination

The diagnosis of RTI’s can be based on three different methods: physical
examination, blood tests, or swabbed cultures.
“Pertinent elements of the physical examination for STDs include palpation
for enlarged or tender lymph nodes, inspection of skin and oral mucosa,
and an external anal and genital examination, including inspection for
discharge, ulcers, or rashes.”
https://www.cdc.gov/immigrantrefugeehealth/guidelines/domestic/sexually
-transmitted-diseases/std-refugee-health-guidelines.pdf
“Some people avoid STI screening due to the discomfort or embarrassment
of having a genital swab. But, today many STIs can be diagnosed with
blood tests, including genital herpes, HIV, syphilis, and hepatitis B. Even
so, STIs like chlamydia, gonorrhea, and trichomoniasis require a swab for
diagnosis.”
https://www.verywellhealth.com/can-i-get-an-std-blood-test-3132740
https://www.verywellhealth.com/urine-testing-for-gonorrhea-and-
chlamydia-3132777
https://medlineplus.gov/ency/article/003750.htm
https://www.healthline.com/health/sexually-transmitted-diseases/getting-
tested

10. Techniques for specimen collection

Genital swabs can be collected from the cervix, external genitalia (such as
the vulva, penis, scrotum…), the vaginal walls, the anus, or from urethral
discharge. This swab is performed while rubbing the swab, in a rotating
motion, against the desired area for 30 seconds. The following step is
performing a smear on a clean glass slide, which is transported and handled
with care until it reaches a laboratory facility.
The following steps for bacterial, fungal and protozoan infections are as
listed:
 PCR amplification – done for nucleic acid probe for detection of
Chlamydia trachomatis and Neisseria gonorrhoeae. [1]
 Gram stain [1]
 Direct immunofluorescence [1]
[1] https://www.rcpa.edu.au/Manuals/RCPA-Manual/Pathology-
Tests/G/Genital-swab~
For viral infections such as HPV and herpes, abnormal cells are collected
via biopsy and can be subjected to the following tests:
 Hybrid capture HPV DNA Test 2 (hc2)
 Viral culture
 PCR tests
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139291/
https://www.mayoclinic.org/diseases-conditions/genital-herpes/diagnosis-
treatment/drc-20356167
It is worthy of note that these lab tests must be done in a certified
specialized lab that can handle these types of (often dangerous)
microorganisms.

11. Treatment
FLUCONAZOLE = broad stroke antifungal medicine
“If you have vaginal candidiasis, likely you will use antifungal medicine to
treat it. Often, the treatment is an antifungal medicine applied inside the
vagina or a single dose of fluconazole taken by mouth. You may need other
treatments if your infection is:
 Is more severe
 Doesn’t get better
 Keeps coming back after getting better”
https://www.cdc.gov/fungal/diseases/candidiasis/genital/index.ht
ml
“The specific type and dose of antifungal medication used to treat invasive
candidiasis usually depends on the patient’s age, immune status, and
location and severity of the infection. For most adults, the initial
recommended antifungal treatment is an echinocandin (caspofungin,
micafungin, or anidulafungin) given through the vein (intravenous or IV).
Fluconazole, amphotericin B, and other antifungal medications may also be
appropriate in certain situations.”
https://www.cdc.gov/fungal/diseases/candidiasis/invasive/treatme
nt.html

[2] “Several drugs can be used to treat Giardia infection. Effective

treatments include metronidazole, tinidazole, and nitazoxanide. Other
medications include paromomycin, quinacrine, and furazolidone. Some of
these drugs may not be readily available in the United States.” [1]
“Trichomoniasis is usually treated quickly and easily with antibiotics. Most
people are prescribed an antibiotic called metronidazole, which is very
effective if taken correctly. You'll usually have to take metronidazole twice
a day, for 5 to 7 days.” [3] “Diagnosis is confirmed by detection of
Entamoeba histolytica antigen or DNA in stool or antibodies against the
parasite in serum. Treatment is with nitroimidazoles (including
metronidazole or tinidazole) followed by luminal agents such as
paromomycin or diloxanide furoate to prevent relapse.” [4] “Liposomal
amphotericin B is FDA-approved for treatment of visceral leishmaniasis
and generally is the treatment of choice for U.S.”
[1] https://www.nhs.uk/conditions/trichomoniasis/treatment/
[2] https://www.cdc.gov/parasites/giardia/medical-
professionals.html
[3] https://bestpractice.bmj.com/topics/en-us/553
[4]https://www.cdc.gov/parasites/leishmaniasis/health_profession
als/index.html
[5] “Treatment for molluscum contagiosum (MC) is not routinely
recommended because most cases clear up on their own in around 6 to 18
months. Treatment is usually only recommended for adults and older
children who have spots that are particularly unsightly and are affecting
their quality of life. Treatment is also be recommended for people with
weakened immune systems, as the condition can take several years to clear
in these cases.” [6] “STIs caused by viruses include herpes, human
papillomavirus (HPV), and HIV. These are usually treated with oral
antiviral or antiretroviral medications. Most viral STIs can be managed but
do not have cures. There are several medications available by prescription
for the treatment of viral STIs:
 Herpes: Acyclovir, famciclovir, valacyclovir
 HPV: Podofilox, imiquimod, sinecatechins
 HIV/AIDS: Antiretroviral medications are used to treat HIV and
AIDS. The proper medication for you will depend on the stage of
your condition. Prescriptions used to treat HIV and AIDS include
enfuvirtide (T20), emtricitabine, tenofovir, abacavir, rilpivirine,
etravirine, efavirenz, dolutegravir, elvitegravir, tipranavir,
lopinavir/ritonavir, darunavir, maraviroc, and ibalizumab.”
[6] The antibiotic prescribed typically depends on the bacteria behind the
infection. Here are common antibiotics prescribed for different infections:2
 Chlamydia: Zithromax (azithromycin), Vibramycin (doxycycline)
 Gonorrhea: Rocephin (ceftriaxone) or, if allergic to it, Gentak
(gentamicin) plus azithromycin
  Syphilis: Penicillin G or, if allergic to penicillin, other antibiotics
such as doxycycline, Sumycin (tetracycline), Moxatag (amoxicillin),
and ceftriaxone
 Chancroid: Azithromycin, ceftriaxone, Cipro (ciprofloxacin)”

[5] https://www.nhs.uk/conditions/molluscum-contagiosum/treatment/
[6] https://www.verywellhealth.com/std-treatment-4014305

ADDITIONAL ADVICE “Once you start treatment, it's necessary

to finish the prescription. If you don't think you'll be able to take
medication as prescribed, tell your doctor. A shorter, simpler
course of treatment may be available.
In addition, it's important to abstain from sex until seven days
after you've completed treatment and any sores have healed.
Experts also suggest women be retested in about three months
because there's a high chance of reinfection.”
https://www.mayoclinic.org/diseases-conditions/sexually-
transmitted-diseases-stds/diagnosis-treatment/drc-20351246

ALL DRUG TREATMENTS:

https://www.aafp.org/pubs/afp/issues/1999/1001/p1387.html

12. Clinical case