THE REPRODUCTIVE SYSTEM IN HUMANS AND RELATED DISEASES
General information about the reproductive system in humans
The biological significance of reproductive system and development of the
1.1 The biological significance of the reproductive system in humans
Reproduction is crucial for all living organisms as it enables the creation of new life and the continuation of species on Earth This essential process occurs within the reproductive organs, which include various sex organs that collaborate to facilitate procreation Given their significant role, many people recognize reproductive systems as the most important organs in the body.
The male reproductive system, primarily located in the pelvic region, plays a crucial role in producing sperm essential for fertilization This system is vital for reproduction as it includes fluids such as hormones and pheromones that support reproductive functions Unlike other bodily systems, the reproductive system varies by sex; the male and female systems possess distinct compositions and functions This sexual differentiation enables the merging of genetic material from two individuals, resulting in the creation of unique offspring.
The male reproductive system consists of three key sections, beginning with the testes, which are responsible for sperm production and storage within the scrotum Immature sperm produced in the testes mature in the epididymis before being released In contrast, the female reproductive system, located in the pelvic area, also comprises three main sections It begins with the vagina, which connects to the vulva and the vaginal opening, leading to the uterus The uterus is crucial as it nurtures the fetus and houses the ovaries, which produce eggs for fertilization.
The vagina connects to the cervix and Fallopian tubes, which link to the ovaries Eggs are released from the ovaries and travel through the Fallopian tubes If fertilization occurs when sperm enters the egg, the resulting fertilized egg may be eliminated through menstruation.
Fallopian tube Human fertilization takes place after internal fertilization has taken place
Fertilization occurs when a female's egg meets a male's sperm during sexual intercourse Once sperm is released into the vagina, it travels through the cervix and into the uterus, where it can fertilize the ovum Successful fertilization initiates the gestation process, which typically lasts around nine months and culminates in labor and the birth of a baby However, the reproductive system can be impacted by various diseases, with cancer being the most prevalent condition that affects its functions.
Cancer can significantly impact the reproductive system in both females and males In women, it primarily affects the uterus, ovaries, and cervix, while men may face testicular, prostate, and penile cancers Timely treatment is crucial, as untreated cancer can damage vital reproductive organs, potentially leading to dysfunction The reproductive system is essential for sustaining life, making its health a top priority.
Figure 1 Organs and structures of the male and female reproductive systems
1.2 Development of the reproductive organs
The sex of a child is established at fertilization when the spermatozoon meets the ovum, with genetic differences between males and females determined by their respective chromosomes Following this genetic determination, a series of changes occurs that ultimately leads to the development of an adult male or female Notably, during the first eight weeks of an embryo's life in the uterus, there are no external indicators of sex; this period is characterized as neutral or indifferent, and the sex can only be identified through chromosomal examination.
The differentiation phase in embryonic development begins with the formation of testes in male gonads, followed shortly by the development of ovaries in female gonads Initially, male and female embryos share similarities, including comparable duct systems that connect the undifferentiated gonads to the exterior and similar external genitalia, represented by three basic protuberances Both embryos possess four ducts, which play a crucial role in establishing the anatomical differences between males and females later in development.
The mesonephric, or Wolffian, ducts are crucial to the development of the urinary system, differentiating into key male structures such as the epididymis, ductus deferens, ejaculatory duct, and seminal vesicle In contrast, these ducts are largely suppressed in females, where the paramesonephric, or Müllerian, ducts persist to form the fallopian tubes, uterus, and part of the vagina Additionally, differentiation of the primitive external genitalia leads to the formation of the penis and scrotum in males, while in females, it results in the vulva, including the clitoris, labia, and vaginal vestibule.
At birth, the sex organs are fully developed and positioned but remain non-functional Abnormalities during embryonic development can result in conditions such as hermaphroditism and pseudohermaphroditism Throughout childhood, reproductive organs grow steadily, leading to gradual activity development Puberty triggers heightened activity in the sex glands and the emergence of secondary sexual characteristics.
In males at puberty the testes enlarge and become active, the external genitalia enlarge, and the capacity to ejaculate develops Marked changes in height and weight occur as
Figure 2 Differentiation of external genitalia in the human embryo and fetus
During puberty, hormonal secretion from the testes increases, leading to the enlargement of the larynx, which results in a deeper voice This period also sees pronounced changes in the skeleton, particularly in the pelvic bones and skull Additionally, there is a noticeable increase in hair growth, with thicker armpit and pubic hair, as well as the development of facial hair and hair on the chest, abdomen, and limbs However, hair at the temples may begin to recede Furthermore, skin glands, particularly apocrine glands located in the armpits, groin, and around the anus, become more active during this time.
During puberty, females experience significant physical changes, including the enlargement of external genitalia and the onset of menstrual cycles as the uterus begins its regular activity Breast development occurs alongside an increase in body fat, shaping the typical contours of a mature female Additionally, there is a notable growth in axillary and pubic hair, which becomes thicker and more abundant.
Male sexual physiology
Figure 3 The male reproductive organs and their associated structures
The functions of the male reproductive organs are:
- Production, maturation and storage of spermatozoa
- Delivery of spermatozoa in semen into the female reproductive tract
The urethra is also the passageway for urine excretion
The scrotum is a pigmented pouch composed of skin, fibrous and connective tissue, and smooth muscle, divided into two compartments Each compartment houses a testis, an epididymis, and the testicular end of the spermatic cord Positioned below the symphysis pubis, the scrotum is located in front of the upper thighs and behind the penis.
The scrotum serves a crucial role in safeguarding the testes while maintaining an optimal temperature for sperm development, which is slightly cooler than the body's normal temperature It features specialized muscles that enable it to contract and relax, adjusting the position of the testicles closer to the body for warmth and protection or further away to facilitate cooling.
Figure 4 The testis A Section of the testis and its coverings B Longitudinal section of a testis and deferent duct
They are about 4.5 cm long, 2.5 cm wide and 3 cm thick and are suspended in the scrotum by the spermatic cords They are surrounded by three layers of tissue
The tunica vaginalis is a double membrane that serves as the outer covering of the testes, originating from the abdominal and pelvic peritoneum In early fetal development, the testes form in the lumbar region of the abdominal cavity, situated just below the kidneys As the testes descend into the scrotum, they carry along with them layers of peritoneum, along with blood and lymph vessels, nerves, and the deferent duct.
6 eventually surrounds the testes in the scrotum, and becomes detached from the abominal peritoneum Descent of the testes into the scrotum should be complete by the
8 th month of fetal life
- Tunaca albuginea This is a fibrous covering beneath the tunica vaginalis Ingrowths from septa, dividing the glandular structure of the testes intio lobules
- Tunica vasculosa This consists of a network of capillaries supported by delicate connective tissue
The testis contains 200–300 lobules, each housing 1–4 convoluted seminiferous tubules where germinal epithelial cells are located Interstitial cells, known as Leydig cells, are situated between these tubules and produce testosterone after puberty At the upper pole of the testis, the tubules merge to form a single, approximately 6-meter-long tubule that is intricately folded and densely packed into the epididymis This structure then extends as the deferent duct (vas deferens) within the spermatic cord, which also carries blood and lymph vessels to the testes.
Spermatozoa, or sperm, are generated in the seminiferous tubules of the testes and mature as they travel through the convoluted epididymis, where they are stored Follicle-stimulating hormone (FSH) from the anterior pituitary gland plays a crucial role in stimulating sperm production A mature sperm consists of a head, body, and a long, whip-like tail that enables motility The head is primarily filled with the nucleus, which houses the DNA and contains enzymes necessary for penetrating the ovum's outer layers to reach and fuse with its nucleus Additionally, the sperm's body is rich in mitochondria, providing the energy needed for the tail's movement, propelling the sperm through the female reproductive tract.
Spermatogenesis, the process of sperm production, requires a temperature approximately 3°C lower than the normal body temperature for optimal success The testes are situated outside the abdominal cavity, which helps to maintain this cooler temperature, while the scrotum's thin outer layer contains minimal insulating fat, further aiding in temperature regulation.
Unlike females, who produce no new gametes after birth, sperm production inmales begins at puberty and continues throughout life, often into old age, under the influence of testosterone
The spermatic cords are essential structures that suspend the testes within the scrotum, comprising a testicular artery, veins, lymphatics, a deferent duct, and nerves These components converge from their abdominal origins to form the cord, which is encased in a sheath of smooth muscle, connective, and fibrous tissues Extending through the inguinal canal, the cord securely attaches to the posterior wall of the testis.
* Blood supply, lymph drainage and nerve supply
Arterial supply The testicular artery branches from the abdominal aorta, just below the renal arteries
Venous drainage The testicular vein passes into the abdominal cavity The left vein opens into the left renal vein and the right into the inferior vena cava
Lymph drainage This is through lymph nodes around the aorta
Figure 6 Section of the prostate gland and associated reproductive structures on one side
Nerve supply This is provided by branches from the 10th and 11th thoracic nerves
Measuring approximately 45 cm in length, the duct ascends from the testis through the inguinal canal and moves medially towards the bladder's posterior wall, where it merges with the seminal vesicle duct to create the ejaculatory duct (Fig 6).
- Structure: The seminal vesicles are two small fibromuscular pouches, 5cm long, lined with columnar epithelium and lying on the posterior aspect of the bladder ( Fig 6)
At its lower end each seminal vesicle opens into a short duct, which joins with the corresponding deferent duct to form an ejaculatory duct
The seminal vesicles play a crucial role in ejaculation by contracting to release seminal fluid, which constitutes 60% of semen's volume This fluid is alkaline, safeguarding sperm in the vagina's acidic environment, and is rich in fructose, providing essential energy for sperm as they navigate the female reproductive tract.
The ejaculatory ducts are two approximately 2 cm long tubes that form from the merging of the duct from a seminal vesicle and a deferent duct These ducts traverse the prostate gland and connect to the prostatic urethra, facilitating the transport of seminal fluid and spermatozoa into the urethra.
The walls of the ejaculatory ducts are composed of the same layers of tissue as the seminal vesicles
The prostate gland is located in the pelvic cavity, positioned in front of the rectum and behind the pubic symphysis, completely encasing the urethra as it exits the bladder This gland features an outer fibrous layer that surrounds glandular tissue, which is enveloped by smooth muscle In youth, the prostate typically weighs around 8 grams, but it gradually increases in size over time.
(hypertrophies) with age and is likely to weigh about 40 g by the age of 50
The prostate gland produces a thin, milky fluid that constitutes approximately 30% of semen's volume, contributing to its characteristic appearance This fluid includes a clotting enzyme that thickens the semen within the vagina, enhancing the chances of retention near the cervix.
The male urethra serves as a dual conduit for urine and semen, measuring approximately 19–20 cm in length and divided into three sections The prostatic urethra begins at the bladder's urethral orifice and traverses the prostate gland Next, the membranous urethra, the shortest and narrowest segment, extends from the prostate to the bulb of the penis, passing through the perineal membrane Finally, the spongiose or penile urethra is located within the corpus spongiosum of the penis and concludes at the external urethral orifice in the glans penis.
The urinary system features two urethral sphincters: the internal sphincter, which consists of smooth muscle located at the bladder's neck above the prostate gland, and the external sphincter, composed of skeletal muscle that encircles the membranous section of the urethra.
Figure 7 The penis A Viewed from below B Viewed from the side
The penis consists of a root that anchors it in the perineum and a shaft, which is the visible and movable part of the organ The shaft is composed of three cylindrical masses of erectile tissue and smooth muscle, supported by fibrous tissue and covered with skin, all supplied with a rich blood supply.
Female sexual physiology
The functions of the female reproductive system are:
- Lactation, the production of breast milk, which provides complete nourishment for the baby in its early life
The vulva, which refers to the external genitalia, comprises several key structures including the labia majora, labia minora, clitoris, vaginal orifice, vestibule, hymen, and Bartholin’s glands.
Figure 9 The female reproductive organs Faint lines indicate the positions of the lower ribs and the pelvis
The vulva is defined by two prominent folds known as the labia majora, which are made up of skin, fibrous tissue, and fat, housing numerous sebaceous and eccrine sweat glands These folds connect at the front near the pubic symphysis and blend into the perineal skin at the back During puberty, hair begins to develop on the mons pubis and the outer surfaces of the labia majora.
These are two smaller folds of skin between the labia majora, containing numerous sebaceous and eccrine sweat glands
The cleft between the labia minora is the vestibule The vagina, urethra and ducts of the greater vestibular glands open into the vestibule
The clitoris corresponds to the penis in the male and contains sensory nerve endings and erectile tissue
Figure 10 The external genitalia of the female
The vestibular glands, also known as Bartholin’s glands, are located on either side of the vaginal opening, each roughly the size of a small pea Their ducts open into the vestibule just next to the hymen's attachment, and they play a crucial role in secreting mucus that maintains moisture in the vulva.
Blood supply, lymph drainage and nerve supply
- Arterial supply This is by branches from the internal pudendal arteries that branch from the internal iliac arteries and by external pudendal arteries that branch from the femoral arteries
- Venous drainage This forms a large plexus which eventually drains into the internal iliac veins
- Lymph drainage This is through the superficial inguinal nodes
- Nerve supply This is by branches from pudendal nerves
The perineum is a triangular region that stretches from the base of the labia minora to the anal canal, composed of connective tissue, muscle, and fat This area plays a crucial role in supporting the pelvic floor muscles.
The internal organs of the female reproductive system lie in the pelvic cavity and consist of the vagina, uterus, two uterine tubes and two ovaries
The vagina is a fibromuscular tube that connects the vestibule at its distal end to the uterine cervix at its proximal end, running at a 45° angle between the bladder in front and the rectum and anus behind In adults, the anterior wall measures approximately 7.5 cm, while the posterior wall is about 9 cm long, with the difference attributed to the angle of the cervix's insertion through the anterior wall.
The vaginal wall consists of three distinct layers: an outer layer of areolar tissue, a middle layer of smooth muscle, and an inner lining of stratified squamous epithelium that forms rugae While it lacks secretory glands, cervical secretions help maintain moisture During the reproductive years, Lactobacillus acidophilus bacteria, which produce lactic acid, are typically present, ensuring the vaginal pH remains between 4.9 and 3.5 This acidity plays a crucial role in inhibiting the growth of harmful microorganisms that may enter the vagina.
- Function: The vagina acts as the receptacle for the penis during sexual intercourse
(coitus), and provides an elastic passageway through which the baby passes during childbirth
The hymen is a delicate mucous membrane that partially covers the vaginal opening, typically remaining incomplete to facilitate menstrual flow It can be stretched or completely torn during sexual intercourse, tampon insertion, or childbirth.
Blood supply, lymph drainage and nerve supply
- Arterial supply An arterial plexus is formed round the vagina, derived from the uterine and vaginal arteries, which are branches of the internal iliac arteries
- Venous drainage A venous plexus, situated in the muscular wall, drains into the internal iliac veins
- Lymph drainage This is through the deep and superficial iliac glands
- Nerve supply This consists of parasympathetic fibres from the sacral outflow, sympathetic fibres from the lumbar outflow and somatic sensory fibres from the pudendal nerves
Figure 11Lateral view of the female reproductive organs in the pelvis and their associated structures
The uterus is a hollow muscular pear-shaped organ, flattened anteroposteriorly It lies in the pelvic cavity between the urinary bladder and the rectum
In most women, the uterus is positioned in an anteverted and anteflexed orientation, creating a near-right angle with the vagina This alignment causes the anterior wall of the uterus to rest partially against the bladder, resulting in the formation of the vesicouterine pouch between these two organs.
In an upright position, the uterus is situated horizontally, measuring approximately 7.5 cm in length and 5 cm in width, with walls that are about 2.5 cm thick Its weight typically ranges between 30 grams.
40 grams The parts of the uterus are the fundus, body and cervix
Fundus This is the dome-shaped part of the uterus above the openings of the uterine tubes
Body This is the main part It is narrowest inferiorly at the internal os where it is continuous with the cervix
Cervix (‘neck’ of the uterus) This protrudes through the anterior wall of the vagina, opening into it at the external os
- Structure: The walls of the uterus are composed of three layers of tissue: perimetrium, myometrium and endometrium
Perimetrium This is peritoneum, which is distributed differently on the various surfaces of the uterus ( Figure 12 )
Figure 12 The female reproductive organs in the pelvis
The peritoneum is folded over the fundus and body of the uterus, extending onto the upper surface of the urinary bladder, which creates the vesicouterine pouch.
Posteriorly the peritoneum covers the fundus, the body and the cervix, then it folds back on to the rectum to form the rectouterine pouch (of Douglas)
The peritoneum creates a double fold at the upper free border of the uterine tubes, covering only the fundus laterally This structure, known as the broad ligament, connects the uterus to the pelvic sides at its lateral ends.
Myometrium This is the thickest layer of tissue in the uterine wall It is a mass of smooth muscle fibres interlaced with areolar tissue, blood vessels and nerves
The endometrium is composed of columnar epithelium overlying a connective tissue layer filled with numerous mucus-secreting tubular glands This tissue is abundantly supplied with blood through spiral arteries, which are branches of the uterine artery Functionally, the endometrium is divided into two distinct layers.
The functional layer, which is the uppermost layer of the endometrium, thickens and develops an abundant supply of blood vessels during the first half of the menstrual cycle If fertilization of the ovum does not occur, this layer is shed during menstruation.
- The basal layer lies next to the myometrium, and is not lost during menstruation It is the layer from which the fresh functional layer is regenerated during each cycle
The cervical canal's upper two-thirds is lined with a mucous membrane, while the lower portion transitions to stratified squamous epithelium, seamlessly connecting with the vaginal lining.
Blood supply, lymph drainage and nerve supply
Arterial supply This is by the uterine arteries, branches of the internal iliac arteries
The lateral aspects of the uterus are supplied by arteries that run between the two layers of the broad ligaments These arteries provide essential blood flow to both the uterus and uterine tubes, and they connect with the ovarian arteries to ensure adequate supply to the ovaries.
Venous drainage The veins follow the same route as the arteries and eventually drain into the internal iliac veins
The diseases related to the reproductive system in humans
Chlamydia
1.1 The symptoms of Chlamydia’ disease
Chlamydia trachomatis is the most common sexually transmitted bacterial infection globally, with the World Health Organization reporting 90 million new cases each year This pathogen is a leading cause of urethritis and cervicitis, and it can lead to serious complications such as pelvic inflammatory disease (PID), ectopic pregnancy, tubal factor infertility, epididymitis, proctitis, and reactive arthritis.
1.2 The causes of Chlamydia’s disease
- C.trachomatis is the major cause of mucopurulent cervicitis (MPC) (Brunham et al.,
Chlamydial infections, particularly chlamydial cervicitis, are frequently linked to urethritis or acute urethral syndrome, as noted by Tamm et al (1980) According to Mardh et al (1977), these infections can result in pelvic inflammatory disease (PID) in women Chlamydial MPC is associated with at least three significant complications, highlighting the importance of early detection and treatment.
(i) ascending intraluminal spread of organisms from the cervix, producing PID
Figure 17 Transmission electron micrograph of C.trachomatis E/UW-5/CX growth in human amniotic epithelial cells
Ascending infections during pregnancy can lead to serious complications such as premature rupture of membranes, chorioamnionitis, premature delivery, and infections in both the mother and newborn.
(iii) the development of cervical neoplasia
Although oncogenic types of human papillomavirus clearly cause most, if not all, cervical carcinomas, C.trachomatis seems to play an important cofactor role ( Paavonen et al., 1998a)
While straightforward criteria such as endocervical mucopus, erythema, edema, and induced mucosal bleeding have been established for the presumptive diagnosis of mucopurulent cervicitis (MPC), many instances of chlamydial cervicitis remain asymptomatic or exhibit only mild symptoms, lacking distinct clinical indicators.
Around 50% of women with chlamydial infection experience it in both the cervix and urethra, while one-third have it solely in the cervix, and about 15-25% are affected only in the urethra.
Chlamydia trachomatis is the leading cause of pelvic inflammatory disease (PID) unrelated to pregnancy or surgical interventions The clinical manifestations of chlamydial PID can vary significantly, ranging from mild endometritis to severe conditions such as salpingitis, tubo-ovarian abscess, pelvic peritonitis, periappendicitis, and perihepatitis Notably, many cases may only represent a small fraction of the total chlamydial infections affecting the upper genital tract, with an increasing number of instances being atypical or asymptomatic.
Nucleic acid amplification tests ( NAAT) must be considered the tests of choice for diagnosing C.trachomatis infection (Black, 1997; Puolakkainen et al., 1998) The
Nucleic Acid Amplification Tests (NAAT) offer highly sensitive diagnostic tests for C trachomatis, surpassing traditional culture and antigen tests Both Polymerase Chain Reaction (PCR) and Ligase Chain Reaction (LCR) target nucleotide sequences in the chlamydial cryptic plasmid, which exists in approximately 7 to 10 copies per elementary body, providing a sensitivity advantage Comparative studies indicate that PCR and LCR yield similar performance for urogenital specimens and urine, with sensitivities exceeding 90% and specificities nearing 100%, resulting in very few false-positive results However, issues with reproducibility have been noted with Amplicor PCR, highlighting the need for careful testing before these amplification methods are implemented in clinical settings.
NAATs offer a significant benefit as they can utilize first void urine (FVU) specimens and self-collected vaginal or vulvar swabs During a pelvic examination, it is recommended to collect a specimen from the cervix However, if a pelvic exam is not conducted, testing a urine specimen can still yield reliable and accurate results.
Although the NAAT are more expensive than the antigen tests, they still should be considered the tests of choice because they will detect many more infectied individuals
Investing in more expensive chlamydia tests is cost-effective due to the high costs associated with managing complications from chlamydial infections The primary objective of Chlamydia screening programs is to detect and treat as many infections as possible The introduction of non-invasive specimen collection methods, which eliminate the need for physical examinations, is expected to significantly enhance Chlamydia control efforts The high prevalence of C trachomatis infections among young populations supports the widespread implementation of screening using nucleic acid amplification tests (NAAT) Optimism surrounds the potential of expanded screening programs to substantially reduce both the incidence and complications associated with genital C trachomatis infections Given that asymptomatic infections are prevalent in sexually active adolescents, routine screening during annual health check-ups is essential, particularly for women aged 20-24 with new or multiple sexual partners who do not consistently use barrier methods However, repeating screenings could decrease the baseline prevalence of C trachomatis, necessitating more targeted approaches to ensure cost-effectiveness in future screening strategies.
1.4 Treatment and prevention of Chlamydia’s disease
New guidelines for the treatment of patients with sexually transmitted chlamydial infection have been recently published (Centers for Disease Control and Prevention,
For the treatment of uncomplicated genital chlamydial infections, recommended regimens include a single oral dose of 1g or doxycycline 100mg taken twice daily for 7 days Alternative options are erythromycin 500mg taken four times daily for 7 days or ofloxacin 300mg taken twice daily for 7 days Azithromycin, prescribed as a single 1g oral dose, is as effective as the traditional 7-day doxycycline regimen It offers superior pharmacokinetic properties, including high bioavailability, reduced gastrointestinal side effects, and enhanced tissue concentration, with a half-life of 5-7 days.
(Rakita, 1998) These characteristics allow for single dosing, which alleviates the problem of patient non-compliance or delayed care with multi-day regimens
Current data on single-dose therapy during pregnancy and conditions like PID is limited However, research indicates that azithromycin is an effective treatment for chlamydial infections in pregnant women when erythromycin or amoxicillin cannot be used Despite its higher cost, azithromycin may be a cost-effective option in high-risk individuals or those with a history of non-compliance The expenses associated with re-treatment due to non-compliance and contact tracing can make single-dose azithromycin more economical compared to doxycycline.
To effectively combat the spread of STDs and HIV, it is essential to promote safer sexual practices and modify risk behaviors Screening for Chlamydia trachomatis is crucial in preventing long-term complications related to pelvic inflammatory disease (PID) Comprehensive Chlamydia control programs should focus on developing high-quality diagnostic services, providing clinical guidelines for managing cervicitis and PID, and identifying asymptomatic carriers Additionally, establishing surveillance systems, training healthcare professionals, and regularly evaluating control measures are vital Routine evaluations of sexual partners and effective patient education on behavioral changes and contraception are also key components of these initiatives.
Disease prevention can be primary, secondary or tertiary:
- Primary and secondary prevention need to be strengthened and integrated into health care systems, and must be accessible to all
- Tertiary prevention of acute and chronic chlamydial infections of the upper genital tract has largely failed because substantial tubal damage has already occurred by the time symptoms develop
Primary prevention aims to reduce the risk of chlamydial infection through lifestyle counseling and health education Clinicians are crucial in this effort by inquiring about risky sexual behaviors, promoting screening for at-risk individuals, ensuring treatment for male partners, and advising on safe sex practices Despite these efforts, the effectiveness of health education in preventing chlamydia has been limited Furthermore, research on the efficacy of primary prevention strategies is often slow and complex.
Universal screening for chlamydial infections is essential for secondary prevention of pelvic inflammatory disease (PID) and its long-term consequences Given their high prevalence and significant morbidity, chlamydial infections meet the criteria for effective screening, as they can be diagnosed and treated Early detection of asymptomatic cases through screening can prevent lower genital tract infections from progressing to upper genital tract infections Recent advancements, such as single-dose azithromycin therapy, nucleic acid amplification tests (NAAT), and first-void urine (FVU) specimens, are expected to enhance prevention efforts However, the impact of these interventions on the incidence of tubal factor infertility remains uncertain Evidence from Sweden indicates that targeted screening can lead to a reduction in C trachomatis infections and PID, subsequently decreasing the rates of ectopic pregnancies.
Gonorrhoea
2.1 The symptoms of Gonorrhoea’s disease
Figure 18.The symptoms of Gonorrhoea’s disease
Gonorrhea is caused by the bacterium Neisseria gonorrhoeae, which infects the mucosal surfaces of the reproductive and urinary tracts In males, it can lead to suppurative urethritis and may spread to the prostate, epididymis, and testes In females, the infection can extend from the vulvar glands, vagina, and cervix to the uterus, uterine tubes, ovaries, and peritoneum, potentially causing fibrosis that obstructs the uterine tubes and results in infertility In males, it may lead to urethral stricture Additionally, non-venereal transmission of gonorrhea can result in neonatal ophthalmia in infants born to infected mothers, as the eyes become infected during passage through the birth canal.
2.2 The causes of Gonorrhoea’s disease
Figure 19 The causes of Gonorrhoea's disease
Gonorrhoea is caused by the bacterium Neisseria gonorrhoeae, which is sensitive to environmental factors like oxygen, temperature, and desiccation, making it difficult to culture and survive outside the human host This fastidious organism relies on the human body for essential nutrients, as many strains have limited biosynthetic capabilities for amino acids It acquires vital iron by binding to host proteins such as transferrin and lactoferrin, stripping them of iron for its growth N gonorrhoeae can thrive in varying oxygen levels found in the male and female urogenital tracts, allowing it to adapt to aerobic, microaerobic, and anaerobic environments within the host.
N gonorrhoeae has the ability to acquire new genetic material through horizontal genetic transfer (HGT), a process that involves the uptake of external DNA from other bacteria, primarily facilitated by type IV pilus-mediated transformation This bacterium remains naturally competent for transformation throughout its life cycle, which plays a significant role in its adaptability and evolution Accurate diagnosis of gonorrhea is crucial for effective treatment and management of the disease.
The incubation period for urogenital gonorrhoea typically spans from 2 to 8 days, with clinical manifestations varying significantly between men and women In men, over 90% with gonococcal urethritis exhibit symptoms such as urethral discharge and dysuria, allowing for effective syndromic diagnosis, which is both time-efficient and cost-effective For symptomatic men, Gram stain can aid in symptom evaluation, whereas laboratory tests are crucial for detecting gonorrhoea in asymptomatic individuals and for identifying extragenital infections across all genders, which often present with nonspecific symptoms In women, although about 40% with gonococcal cervicitis may experience abnormal vaginal discharge, this symptom is not reliable for syndromic diagnosis due to the prevalence of other common genitourinary infections that exhibit similar symptoms.
Diagnosing gonorrhoea microbiologically can be difficult, particularly in areas lacking laboratory resources, which often leads to reliance on syndromic management algorithms for empirical antimicrobial treatment The microbiological diagnosis involves identifying Gram-negative diplococci in stained smears.
34 microscopy, culture of N gonorrhoeae and/or nucleic acid amplification tests (NAATs) detecting N gonorrhoeae DNA or RNA
In resource-limited settings, light microscopy using Gram-stained samples is often the primary method for presumptive diagnosis of N gonorrhoeae infection The sensitivity and specificity of the Gram stain can vary significantly, with the highest accuracy observed in symptomatic males' urethral swabs (sensitivity of 89% to >98% and specificity over 95%) However, sensitivity drops to 40-50% in urethral specimens from asymptomatic males and in endocervical or urethral samples from women, likely due to lower bacterial loads and the presence of other bacterial species The Gram stain is ineffective for diagnosing N gonorrhoeae in pharyngeal and rectal specimens, where sensitivity is ≤ 40% An alternative methylene blue staining method has shown comparable sensitivity and specificity for diagnosing gonococcal urethritis in men.
Prior to the advent of nucleic acid amplification tests (NAATs), culture of Neisseria gonorrhoeae was the gold standard for diagnosis and remains the sole low-cost method in some settings It is essential for test-of-cure in treatment failures, cases of sexual abuse, and evaluating pelvic inflammatory disease (PID) Complete antimicrobial resistance (AMR) testing requires cultured samples, with culture performance influenced by factors such as the anatomical site, specimen collection methods, and transport conditions Cultures taken too soon after exposure may yield false negatives, necessitating repeat testing Urogenital cultures have a sensitivity of 72% to 95%, which can reach 95-100% in experienced settings, while pharyngeal and rectal cultures exhibit significantly lower sensitivity Presumptive identification of N gonorrhoeae is typically achieved through colony appearance, Gram staining, and the oxidase test, while definitive identification may involve immunological tests, sugar utilization tests, NAATs, or mass spectrometry techniques like MALDI-TOF.
Spectrometry tests are essential for distinguishing N gonorrhoeae from other Neisseria species, including N meningitidis and N lactamica, which may also grow on selective culture media, particularly in the pharynx For genomic analysis, DNA extraction from cultured isolates remains the most effective method, as clinical specimens often lack adequate DNA or contain excessive DNA from other bacteria or human cells Additionally, the purification of genomic DNA from clinical specimens has yet to be adequately developed or standardized.
NAATs have become the preferred diagnostic test for STIs due to their noninvasive specimen collection methods, such as urine or self-collected vaginal swabs They do not require viable organisms for detection, allowing for easier transportation and storage NAATs offer superior sensitivity and high specificity, although these can vary based on the type of NAAT and the anatomical site tested Additionally, they provide rapid results, with many newer platforms enabling high throughput and automation Many NAATs can also simultaneously detect other STI-associated pathogens, particularly Chlamydia trachomatis Initially, various in-house, PCR-based NAATs were utilized locally and are still employed as confirmatory tests or for diagnosis in resource-limited settings, targeting conserved gene regions in Neisseria gonorrhoeae, such as the porA pseudogene, opa genes, gyrA, cppB, and methyltransferase genes.
Numerous studies suggest that various nucleic acid amplification tests (NAATs) offer greater sensitivity and maintain high specificity compared to traditional culture methods for diagnosing N gonorrhoeae in pharyngeal and rectal specimens However, it is crucial that these tests undergo thorough local performance evaluations, and a confirmatory NAAT targeting a different genetic sequence should be employed for these specimens This is essential to avoid misidentification of other Neisseria species, which are commonly found in the pharynx and may be confused with N gonorrhoeae.
The development of rapid point-of-care tests (POCTs) for gonorrhoea is crucial for providing definitive diagnoses and guiding specific treatments, especially in settings limited to syndromic management or where patients may not return for follow-up care While the Gram stain is a commonly used POCT with its own benefits and limitations, other innovative tests have emerged, including lateral flow immunochromatographic tests and optical immunoassays that detect antigens, along with the near-POCT NAAT known as the Xpert CT/NG assay.
2.4 Treatment and prevention of Gonorrhoea’s disease
The urgent need for a gonococcal vaccine arises from the global threat of untreatable gonorrhoea exacerbated by antimicrobial resistance (AMR) Developing an effective vaccine is challenging due to the unique biology of the gonococcus, which includes limited adaptive immune responses, a lack of known correlates of protection, and significant antigenic variability among potential vaccine candidates Additionally, the presence of blocking antibodies can hinder the efficacy of bactericidal antibodies targeting conserved antigens, and there is a lack of suitable small laboratory animals for vaccine testing The MeNZB vaccine demonstrated reduced rates of gonorrhoea diagnoses and hospitalizations, providing valuable insights for future vaccine development Although MeNZB is no longer available, the licensed 4CMenB vaccine (BEXSERO) shares components with MeNZB and includes three recombinant meningococcal antigens that are relatively conserved in comparison to their gonococcal counterparts Ongoing research aims to uncover the specific antigens and mechanisms behind MeNZB's protective effects against gonorrhoea, which is essential for advancing gonococcal vaccine development.
Figure 20 Prevention of N.gonorrhoea infections
Research indicates that while mice produced serum bactericidal antibodies against the gonococcus, human sera from those immunized with 4CMenB did not exhibit bactericidal activity against N gonorrhoeae These results highlight significant differences in immune responses between species, emphasizing the need for further immunobiological studies.
N gonorrhoeae immune suppressive responses and how they can be overcome), antigen discovery and animal modelling, are promising for vaccine development
Effective prevention strategies for gonorrhea and other STIs focus on educating individuals about both symptomatic and asymptomatic infections Key initiatives include promoting safe sexual practices, such as increased condom use through targeted education and campaigns Additionally, behavior change communication programs encourage reducing unknown, casual, and unprotected sexual encounters while fostering early health-seeking behaviors Improved sexual partner notification and treatment, along with expanded targeted interventions like screening for vulnerable populations—including sex workers, men who have sex with men (MSM), adolescents, and STI patients and their partners—are also essential components of a comprehensive prevention approach.
Syphilis
3.1 The symptoms of Syphilis’s disease
The primary stage of syphilis is marked by the presence of a classic chancre, which is a painless, ulcerated lesion with a flat base and a raised, firm red border, measuring between 0.5 to 2 cm in diameter In individuals infected with HIV, multiple chancres may develop In women, the chancre typically appears at the entry point of the genital tract and is often accompanied by painless, nonsuppurative inguinal adenopathy in about 80% of cases, usually of regional origin Due to the asymptomatic nature of the chancre and its common location, it frequently goes unnoticed in women.
Even without treatment, the chancre spontaneously heals in 3 to 6 weeks, an indicator of an adequate host immunologic response (Sheffield and Wendel, 1999)
Untreated women with primary syphilis may progress to secondary syphilis, also known as the spirochetemia stage, occurring 4 to 10 weeks after the initial chancre This stage is characterized by the systemic spread of spirochetes to various organ systems, with dermatologic symptoms affecting 90% of infected women and constitutional symptoms, such as low-grade fever, pharyngitis, malaise, arthralgias, and myalgias, present in 70% of cases Additionally, around 40% of adults may show abnormalities in their cerebrospinal fluid, indicating that the central nervous system is also commonly affected during this stage.
(1) A maculopapular rash, usually nonpruritic, starting on the trunk and extending to the proximal extremities with spread to the entire body including palmar and plantar target‐like lesions
(2) Mucous patches which are silver to gray superficial erosions of the genital, anal, and/or oral mucosa
(3) Condylomata lata, which appear as gray plaques in moist intertriginous areas such as the labia majora and minora
Secondary syphilis, often referred to as "The Great Imitator," can impact various organ systems in women, leading to a range of symptoms Conditions such as hepatitis, gastritis, anterior and posterior uveitis, interstitial keratitis, optic neuritis, otosyphilis, skeletal involvement, and neurosyphilis have all been documented in female patients with this stage of syphilis.
In the absence of treatment, the symptomatology of secondary syphilis resolves within
Latent syphilis occurs 2 to 6 weeks after infection and is divided into early latent (less than 12 months) and late latent (more than 12 months) phases In the early latent phase, about 20 to 25% of women may experience recrudescence, while relapses are rare in the late latent phase, and patients are not considered contagious through sexual transmission Vertical transmission can occur in both early and late latent syphilis, though the rates are significantly lower compared to primary and secondary syphilis During the latent stages, serologic tests remain positive, but there are no clinical manifestations present.
Tertiary syphilis affects about one third of untreated patients and typically develops years after the initial infection Due to public health measures and the slow progression of the disease, tertiary syphilis is rare among reproductive-age women Among those who do develop tertiary syphilis, half experience late benign syphilis characterized by gummas, which are destructive granulomatous lesions impacting various organs, including skin and bone The other half includes one fourth with cardiovascular syphilis, marked by medial necrosis of the aorta leading to saccular aneurysms, and the remaining quarter suffers from neurosyphilis, resulting in symptoms like general paresis, tabes dorsalis, optic atrophy, and meningovascular syphilis A distinctive feature of neurosyphilis is the Argyll-Robertson pupil, which does not react to light but accommodates.
Neurosyphilis, a form of tertiary syphilis, can manifest at any stage of syphilis infection, leading to inflammation and obliteration of arteries that supply vital tissues, ultimately resulting in their destruction (Sheffield and Wendel, 1999; Duff, 2014).
Congenital syphilis is transmitted from an infected mother to her fetus during pregnancy The CDC has conducted an analysis of national surveillance data to monitor the rates of congenital syphilis in the United States over different time periods.
Early congenital syphilis manifests with symptoms such as a maculopapular rash that leads to desquamation, hepatosplenomegaly, osteochondritis, snuffles, and iritis If congenital syphilis remains undiagnosed or inadequately treated, late congenital syphilis may emerge, characterized by the classic triad of Hutchinson's teeth, interstitial keratitis, and eighth-nerve deafness Additional complications can include saddle nose, saber shins, seizures, and cognitive impairments.
Figure 21 The symptoms of Syphilis's disease
3.2 The causes of Syphilis’ disease
Syphilis is caused by the bacterium Treponema pallidum subsp pallidum (T pallidum), which was discovered in 1905 by Schaudinn and Hoffmann This microaerophilic, spiral-shaped spirochete is motile and environmentally fragile, measuring 6-20 µm in length and 0.1-0.2 µm in diameter Due to its narrow size, T pallidum cannot be seen using standard bright-field microscopy but can be visualized with special staining techniques Although it cannot be continuously cultivated in vitro, it can be propagated through intratesticular infection in rabbits, which serve as the preferred animal model for research.
Phase-contrast and dark-field microscopy are essential techniques for detecting T pallidum in genital or cutaneous lesions of patients with early syphilis, with silver staining also being a valuable method.
The cellular architecture of T pallidum is similar to that of Gram-negative bacteria It has an outer membrane (OM), a thin peptidoglycan cell wall and an inner membrane
Unlike Gram-negative bacteria, T pallidum has flagella located in the periplasm, and its outer membrane (OM) lacks lipopolysaccharide (LPS), making it more vulnerable to physical and chemical disruptions Freeze-fracture electron microscopy reveals that T pallidum's OM contains only a limited number of integral membrane proteins Some of these treponemal rare outer membrane proteins (TROMPs) are present on the cell surface, suggesting their significance in infection and potential as vaccine targets However, the delicate nature of the T pallidum OM has complicated the definitive identification of TROMPs.
The complete genome sequence of T pallidum Nichols, determined in 1998, has significantly advanced our understanding of this spirochete's metabolism and physiology The genomes of Nichols and other sequenced strains, such as SS14 and Chicago, measure approximately 1.14 Mbp, encode around 1,000 proteins, and lack common genetic elements associated with horizontal gene transfer This small genome size reflects T pallidum's limited biosynthetic capabilities, contributing to its long generation time of 30-33 hours in vivo, sensitivity to environmental conditions, and reliance on host nutrients Notably, T pallidum has a multigene family encoding 12 paralogous proteins known as T pallidum repeat proteins (TprA-TprL), whose functions and locations are debated However, the genetic sequences for TprE, G, and J proteins show stability within strains but variability among them, making them valuable for molecular typing alongside other genomic targets.
The TprK protein is the most variable of the Tpr proteins with several variants typically observed within a strain as a result of a gene conversion mechanism Antigenic
41 variation of the TprK protein during infection may promote chronic infection via immune evasion
Treponema pallidum, the bacterium responsible for syphilis, cannot be cultured in vitro for extended periods, leading to the development of alternative screening and diagnostic tests Clinicians primarily utilize two main testing approaches for laboratory diagnosis: direct detection methods and serologic tests.
The rabbit infectivity test (RIT) is the most sensitive method for diagnosing syphilis, involving the intratesticular injection of infectious tissue into a rabbit, followed by the serial passage of lymphatic products to a second rabbit to confirm the presence of T pallidum spirochetes Additionally, Darkfield microscopic examination is effective in identifying spirochetes in the early stages of the disease using exudate from lesions, utilizing a Darkfield condenser for visualization.
The direct fluorescent antibody test for lesions utilizes touch preparations with immunostaining, while polymerase chain reaction (PCR) of lesion exudates has recently shown higher diagnostic accuracy than dark-field detection in primary lesions (Gayet-Ageron et al., 2015) The effectiveness of PCR in other specimens, such as blood and cerebrospinal fluid, remains under investigation.