Everything about Chlamydia Trachomatis totally explained
Chlamydia trachomatis, an
obligate intracellular human pathogen, is a bacterial species in the genus
Chlamydia, family
Chlamydiaceae, class
Chlamydiae, phylum
Chlamydiae, domain
Bacteria.
C. trachomatis can't be stained with the
Gram stain.
C. trachomatis was the first chlamydial agent discovered in humans. It was identified in 1907.
It comprises three human
biovars:
Urethritis (
serovars D-K),
trachoma (serovars A, B, Ba or C) and
lymphogranuloma venereum (LGV, serovars L1, 2 and 3)).
Many, but not all,
C. trachomatis strains have an extrachromosomal
plasmid.
Chlamydia Trachomatis--- A Silent Disease
Chlamydia trachomatis (CT) infection is the most prevalent sexually transmitted disease in the world, surpassing gonorrhoeal neisseria and syphilis. This study pertains to CT of serovar A to K and L1 to L3. CT infection is the leading cause of non-gonococcal urethritis (NGU). Its diagnosis is usually based on exclusion of gonococcus infection because it's easier to diagnose gonococcus infection clinically and in the laboratory. CT’s infection is sublimed, low level and non-specific symptoms and signs caused it to be very difficult to detect. In many instance, the affected has no symptom or sign that would alert them, to be seriously concern, and take action to seek medical help. It frequently co-exists with gonorrhoeal causing its symptoms to be masked. The successful treatment and elimination of gonorrhoeal from the patient may then appease everyone with the false premise of successful cure but in fact CT infection continues to lurk surreptitiously causing much destruction in many organs. Sexually transmitted disease in this case isn't limited to infection of reproductive organs; it can also cause perihepatitis, periappendicitis, perisplenitis and perinephritis. Serovars A to K can also cause blindness, proctitis and arthritis. Serovars L1-L3 cause lymphogranuloma venereum (LGV) with lymphangitis and lymphadenitis; the resultant obliteration of lymphatic drainage, chronic edema, and stricture formation can cause disfiguring elephantiasis. CT infection can remain dormant or retains low-level activity causing progressive destruction and scarring for many years without being noticed.
Diagnosis of CT infection using urine sample is less invasive and painful than urethral swaps, especially in males, hence it's more acceptable and less traumatic to the potential sufferer. Diagnosis was indeed more painful than the cure. Polymerase chain reaction and ligase chain reaction are assays using urine samples; these assays require about 8 hours but show sensitivity of 86 to 98% with specificity between 99 and 100% [3]
Treatment is relatively simple. In most instances one oral dose of one gram of azithromycin is recommended for treatment of infection by CT infection serovar A to K. Erythromycin can be used if the patient is pregnant. For the treatment of LGV a 21 days regime of doxycycline is recommended, replacement with erythromycin during pregnancy should be used for the same period.
INTRODUCTION
This is a study of the prevalence of Chlamydia trachomatis (CT) infection as an epidemic, an attempt to search and explore medico-social reasons for its silent position, and paradoxically, the most common sexually transmitted disease. Although CT infection bacteria are not as deadly as the human immunodeficiency virus but it's nevertheless extremely destructive to multiple organ systems in the body resulting in severe disabilities culminating in eventual death. Highest infection rate in Latvia is in the age group between 20 to 24 years old with male predominance in between 2003 to 2004 (Appendix II). This is the age group of highest productive value to society; additionally they're at the peak of sexual reproductive life. Infection in this age group causes the most damage to the Latvian society financially and demographically.
In 1993, almost fourteen years ago, Domeika M and Mardh P-A identified CT infection as the most common cause of non-gonoccocal urethritis (NGU) in men as well as the cause of half of all acute epididymitis in men younger than 35 years old. Presently, information available on the internet, www. chlamydia.com identified CT infection as the “Silent Epidemic”. It is reported that CT infection is the most prevalent sexually transmitted disease with 3-4 million new cases each year. The deafening silence is in its lack of symptoms in more than 50% of affected individuals. It is reported in the Pregnancy Information Network that 75% of women and 50% of men infected with CT infection have no symptoms. Moss T.R. reported in 2001 that CT infection pelvic inflammatory disease (PID) in Doncaster England is about five times more common than gonococcus PID [22]. CT infection is now also the most common sexually transmitted disease in the United Kindom [38i]. Prevalence in young adult population of the United States is regarded as high with the highest among black women; racial/ethnic disparities was regarded as substantial [21]. Statistics from health authorities in Latvia identified 820 CT cases per 100,000 population, but only 483 syphilis per 100,000 in population and 746 gonorrhoeas per 100,000 populations in the year 2006 (Refer to Appendix 1). In 2005, there are 729 of CT per 100,000 population compared with 443 syphilis per 100,000 population and 694 gonorrhoea per 100,000 population; consequently, CT can easily be identified as the most prevalent disease in Latvia for the past two years. Increase in incidence is about 20 percent over five years from 2001 to 2005 and an increase of 40 percent in the year 2005. However, if more than 50% of affected individuals don't have symptoms, it's anticipated that these statistical representations is only the tip of the iceberg; perhaps the medical fraternity has been appeased by the lack of warning alarms and the ease of elimination of this bacteria. It is estimated that about one third of sexually transmitted diseases are in those less than 19 years old and prevalence of CT infection in that age group is about 25% [1] The aim of this study is to portray the complexity involved in diagnosing CT infection as well as highlighting the intrinsic difficulty in accurately capturing statistical representation of CT infection in clinical settings.
Graphic representation of Syphilis, Gonorrhoea and Chlamydia infections in Latvia from 1992 to 2006. (Refer to Appendix I)
For the past 15 years:
CT infections --- 1st position 5X, 2nd position 7x, 3rd position 3x. Total patients 23662. 1st position for past 2 years.
Syphilis infections --- 1st position 8x, 2nd position 1x, 3rd position 6x. Total patients 19839.
Gonorrhea Neisseria infections--- 1st position 2x, 2nd position 7x, 3rd position 6x. Total patients 24595
Chlamydia usually occurs currently with gonorrhoeae hence combined total would be 48257 with an average of 24128 patients; this represents 22% more than syphilis.
Table 1: Prevalence of Chlamydia trachomatis Reflection
Year Source Prevalence Statements
1993 Domeika et al [8] CT infection is the most common causes of NGU
2001 Moss TR [22][38i] CT infection PID is 5X more common than Gonoccocal PID
2004 CDC USA CT infection Incidence more than 2X greater than gonorrhoeal (929462/330132)
2005 Latvia Infectious Disease Data CT infection incidence increase by 20% over 5 years from 2001-2005
2004 CDC USA Incidence CT infection in women increase from 1987 at 78.5 per 100,000 to 485 per 100,000 population
2006 Latvia Health Authorities Statistics CT infection 820 per 100,000, Gonorrhoea 694 per 100,000, Syphilis 483 per 100,000
2006 Venkatesh MP et al CT infection is the most common cause of sexually transmitted genital infection
2007 www. netdoctor.co.uk (Dr. A. Robinson)
CT infection is the most common sexually transmitted disease in the UK
2007 www. plannedparenthood.org/sexual-health/std/chlamydia.htm CT infection is the most common STI in USA
BIOLOGICAL DEFINITION
What is Chlamydia trachomatis?
Chlamydia trachomatis is an obligate, gram-negative eubacteria that grows intracellularly by binary fusion. It produces no spores but has a complex metabolic mechanism utilizing amino acids and generally carbohydrates. Chlamydia can infect both vertebrate and nonvertebrate hosts such as humans, animals, birds and plants. The taxonomy of CT infection is shown in Figure 1 as below:
Order : Chlamydiales
Family : Chlamydiaceae
Genus : Chlamydia
Species: ChlamydiaTtrachomatis
: Chlamydia Psittaci
: Chlamydia Pneumoniae
Figure 1. Taxonomy of chlamydia organisms [8]
Chlamydiales is a prokaryotic bacterium with two specialized cell forms: one is elementary body (EB); the other is reticulate body (RB). CT, like some bacteria, possesses a thin cell wall; overall size is between 0.2 to 0.4um; within its cell wall, it contains both deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). It has its own metabolism but unable to produce energy substrates such as phosphorylated nucleoside C10H16N5O13P3 of adenine (ATP). An obligate intracellular energetic parasite, it obtains ATPs from its host. EB is the matured infectious form that can exist intracellarly and survives extracellularly as well, but it's metabolically passive. RB is the immature form, metabolically active but non-infectious, existing only intracellarly within the host cell. Chlamydia display high level of infectious adaptation, tissue tropism, to be able to cause a variety of conditions under different environments, varying from chronic conditions in the eye to acute genital tract or external genitalia infections. It can grow in highly oxygenated environments of the respiratory tract, almost bactericidal hostile environment such as the oral cavity and even in highly chemically active organ of detoxification such as the liver causing perihepatitis.
Chlamydia trachomatis reproductive phases [8]
Phase 1
About 7 to 10 hours post-infection, EB penetrated into the cell cytoplasm and started to form inclusion bodies. This organism begins forming chlamydia antigen and RNA. At the same time, host DNA synthesis is suppressed. This phase can be confirmed by the use of acridine orange staining red demonstrating the presence of RNA. This phase is non-infectious.
Phase 2
After about 14 to 22 hours, large reticulate bodies can be seen. Both RNA and DNA continued to be formed. This phase can be demonstrated by the presence of green-orange cytoplasmic inclusion bodies (DNA) stained by acridine orange. It is considered infectious during this phase from about 20-22 hours post infection. The infectious EB, after being phagocytosed by the host cell, develops into a vacuole in the cytoplasm transforming into an RB that's metabolically active; this provides the energy to replicate more RB by binary fusion producing the next generation of infectious EB. This new generation of EB are released from the infected host by extrusion or by autolysis.
Phase 3
This part of the life cycle is dominated by the presence of elementary bodies (EB). RNA synthesis and protein continue to decrease; eventually it's dominated by the presence of DNA, demonstrated by staining green with acridine orange.
SCOPE OF THIS DISCUSSION
Although the genus of chlamydia consist other separate species causing a variety of disseminated infections, mainly in respiratory tracts, present interest of this paper is focused on Chlamydia trachomatis (C.T). However, CT is the main species with a variety of serotypes causing infections in many different host cell environments presenting as inflammatory disease in various organs.
APPROACH
In order to understand the CT infection problem it's important to study and demonstrate the specific areas of problems encountered, in order to explain why CT is so elusive and difficult to diagnose, detect and treat. It is important to scrutinize how CT managed to elude the vast medical network of laboratory tests, scientific investigations such as laparoscopy and ultrasound, as well as understand why it's so difficult to diagnose its various symptomatic manifestations. Other causes of NGU are ureaplasma, urealyticum, trichomonas vaginalis and HSV but diagnosis of these organisms are clinically equally as elusive. Leukocytic urethral exudates are also present hence their diagnosis is also based on exclusion of gonorrhoeal by gram stain or culture [5].
Chlamydia trachomatis as an infective agent is illustrated here, beginning from its reproductive onset, mode of transmission and its manifestations in its many disease forms in the males, females and neonates. In order to fight its propagation, every physician should critique each step in an attempt to find its deficiencies; in the process, endeavours should be made to identify any loophole that enable CT to remain as the most common sexually transmitted disease. CT infections didn't become the most common sexually transmitted disease by accident. It will remain in that position unless someone awakens any complacency as well as pinpoint the deficiencies.
It is only through academically examining epidemiological CT infection processes, by examining and walking through, meticulously critiquing and highlighting deficiencies in the disease- identification processes, laboratory testing procedures as well as diagnostic equipment used, can the effort of tackling this serious infection be properly addressed. This study can't cover the entire spectrum of the chlamydiales order; it's too big. This study only attempts to draw attention to the fact that CT infections have remained the number one sexually transmitted disease, almost world-wide, for too long and at the same time hopefully identify some loopholes or reasons as to what have been the problems in our approach, in enabling CT to remain in the number one position all these years with signs of ongoing increase demographically and prevalence.
DETAILS:
1. CT Infections In Both Sexes:
A. Theory on Trachoma, Conjunctivitis, Keratitis, Proctitis
Trachoma is characterized as a chronic contagious conjunctivitis marked by inflammatory granulations on the surface of the conjunctiva surface. This is caused by Chlamydia trachomatis serotypes A, B, Ba and C. However, occasionally serotypes D and E have been involved. It is reported by the International Trachoma Initiative, sponsored by Bill Gates, that about eight million people world wide is blinded by this microbe; eighty four million people are suffering active infection. This represents about 10% of the population of this world. The World Health Organisation (WHO), in 1998 adopted a resolution for the Global Elimination of Trachoma by the year 2020. A purulent discharge can be observed from the eye infected with CT infection [27]. Patients affected don't become blind immediately; after some years of chronic eye infection, conjunctivitis, it caused eyelashes to grow inward, scratching the cornea repeatedly. These repeated cornea irritations, keratitis, caused the slow and painful blinding process from childhood to complete blindness in adulthood.
Proctitis or proctocolitis is defined as inflammation of the anus and rectum. CT infection can cause inflammation of the anus in both sexes especially when they practise anal sexual contacts; however, children may become infected by CT infection in the anus during the birthing process or through sexual abuse. Constitutional symptoms are common in conjunction with regional lyphadenopathy including chills, fever, headache, meningismus, anorexia, myalgias and arthralgias. Associated conditions such as septic meningitis, meningoencephalitis, conjunctivitis, hepatitis and skin conditions such as erythema nodosum are also possibly manifested. Proctitis is usually caused by serovar D-K or LGV. Proctitis infection that's non-LGV, are limited to the distal rectum. Mild rectal pain, mucous discharge, tenesmus with occasional bleeding usually presents as the most common symptoms [5]. However, LGV proctitis is usually more severe with ulcerations similar to Crohn’s disease or Herpes Simplex virus infections. Giant cells are produced together with granulomas. Rectal infections untreated can cause perirectal abscess, fistulas in the anus as well as recto-vaginal, recto-vesical and ischio-rectal. Rectal stricture is usually a result of late complications of ano-rectal infection usually it develops about 2 to 6 centimetres from the anal orifice [5].
Problem Analysis:
Of course, systemic CT spread is also possible. CT infection, being a contagious disease, can possibly be transmitted through other forms of social contact similar to trachoma infections but documented incidences are not overwhelming. This is an important avenue for social infection control. Widespread reinforcement of good social hygiene habits such as proper hands washing techniques after toilet use or contact with bodily fluids. Vigilance in preventing fluid exchange in sexual contacts as well as prophylactic use of antibiotic ointment or drops may be the avenue of prevention.
Trachoma can be spread by infected person’s hands or clothing. Educating the public in infectious disease control and hygiene is therefore paramount in control of trachoma. Chlamydia may be transmitted by flies landing on a new host, after being in contact with discharge from the infected person’s nose or eyes. This isn't commonly known. In addition, classification of CT as a well-known sexually transmitted disease can cause physicians as well as the public to neglect this other cause of CT transmission and infection.
B. Theory on Reiters Syndrome
Reiter's syndrome is CT infection that causes three seemingly unrelated symptoms: arthritis, redness of the eyes, and urinary tract signs. Reiter’s syndrome is most often contracted through sexual contact, caused by CT infection; nevertheless, not every person who contracted CT infection develops this syndrome. The reason for this disparity is entirely unknown. Only 6 percent of people with this syndrome don't have gene HLA B27, but 80 percent of people with this syndrome is positive for HLA B27 gene. According to Cecil’s Book of Medicine, other gastrointerstinal bacteria such as Salmonella, Shigella, Yersina and Camphylobacter may also cause Reiter’s Syndrome [2]. The subsequent development of Reiter’s Syndrome, as a result of these other bacteria infections, are also related to HLA B27 [5]. Reiter's syndrome is sometimes referred to as a seronegative spondyloarthropathy because it's one of a group of disorders that cause inflammation throughout the body, particularly in parts of the spine and at other joints where tendons attach to bones; usually the knees and ankles are involved asymmetrically [2]. Examples of other seronegative spondyloarthropathies include psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel syndrome arthritis. Inflammation is a characteristic reaction of tissues to injury or disease and is marked by four signs: swelling, redness, heat, and pain. The infection is most commonly passed from one person to another by sexual intercourse. Concurrent cystitis, with clear mucoid discharge in the male as a characteristic sign, may be the only symptom discovered. This form of the disorder is sometimes called genitourinary or urogenital Reiter's syndrome; nevertheless, symptoms are not restricted to the urogenital system. Conjunctivitis and arthritis or entheropathy may also concurrently be present. Another form of the disorder, called enteric or gastrointestinal Reiter's syndrome, develops when a person eats food or handles substances that are tainted with the bacteria. Reiter's syndrome is also referred to as reactive arthritis, which means that the arthritis occurs as a "reaction" to an infection that started elsewhere in the body. Generally, an increase in cell mediated and humoral response to CT infection antigen can be demonstrated in those with Reiter’s syndrome. Septic arthritis by CT infection can be asymptomatic but gonoccocal as the same site has more symptoms [5]. In many patients, the infection begins in the genitourinary tract such as the bladder, urethra, penis, or vagina. Reiter's syndrome often affects the urogenital tract, including the prostate, urethra, and penis in men and the fallopian tubes, uterus, and vagina in women. Men may notice an increased need to urinate, a burning sensation when urinating, and a discharge from the penis. Some men with Reiter's syndrome develop prostatitis, an inflammation of the prostate gland. Women with Reiter's syndrome also develop signs in the urogenital tract, such as cervicitis or urethritis, which can cause a burning sensation during urination. In addition, some women also develop salpingitis, an inflammation of the fallopian tubes [6] or vulvovaginitis. These conditions may cause very mild symptoms, sometimes simply ignored by the patient; or it may not cause any symptoms at all. Mucocutaneous lesions are characteristic in 70% of males with CT infection in the urethra resulting in nondiarrheal [5]. The arthritis associated with Reiter's syndrome typically affects the knees, ankles, and feet, causing pain and swelling. Wrists, fingers, and other joints are less often affected. Patients with Reiter's syndrome commonly develop inflammation where the tendon attaches to the bone, a condition called enthesopathy. Enthesopathy may result in heel pain and the shortening and thickening of fingers and toes. Some people with Reiter's syndrome also develop heel spurs, bony growths in the heel that cause chronic or long-lasting foot pain (www.healthlink.mcw.edu).
Arthritis in Reiter's syndrome can cause spondylitis or sacroiliitis. Patients with Reiter's syndrome who have the HLA-B27 gene have a greater chance of developing sacroiliitis and spondylitis. It may well be possible that someday gene therapy may prevent CT infections.
Conjunctivitis, an inflammation of the mucous membrane that covers the eyeball and eyelid, develops in about 50 percent of people with urogenital Reiter's syndrome and 75 percent of people with enteric Reiter's syndrome [2]. The cause of such disparity is again unknown. Some may develop uveitis. Conjunctivitis and uveitis can cause eye pain and irritation, and blurred vision. Eye involvement typically occurs early in the course of Reiter's syndrome, and symptoms may be sporadic. The conjunctivitis is usually mild, non-catarrhal, bilateral with inflammation of the bulbar and palpebral [2]. Chronic inflammation of the eye may then develop into trachoma and subsequent chronic irritation from inward turning eyelashes cause the blindness because of damage to the cornea.
About 20 to 40 percent of men with Reiter's syndrome develop small, shallow, painless sores or lesions, called balanitis circinata, on the end of the penis; a differential diagnosis can be made against syphilitic ulcers would be laboratory based, proving presence of spirochetes in the syphilitic ulcers. A small percentage of men and women develop rashes of small hard nodules on the soles of the feet, and less often on the palms of the hands or elsewhere. These rashes are called keratoderma blennorrhagica. In addition, some people with Reiter's syndrome develop mouth ulcers that come and go. In some cases, these ulcers are painless and go unnoticed. This lack of symptom is another significant reason for the lack of concerted effort against CT infections. Our medical model is initiated by patient demands, when there's a lack of symptom there's no demand; hence CT continues to flourish.
About 10 percent of people with Reiter's syndrome, usually those with prolonged disease, develop heart problems including aortic regurgitation and pericarditis. CT infection has also been associated with graft verses host disease and interstitial pneumonitis [17] (National Institute of Arthritis and Musculoskeletal and Skin Diseases).
Problem Analysis:
Vigilance and alertness of general physicians are important when consulted by patients presenting with this triad of symptoms. Physicians should be alert to seek further signs and symptoms; not all these signs present simultaneously nor would they present with equal severity causing the patient to complain at the same time. Dismissal of the patient with antibiotics treatment for simple urinary tract infection is inadequate for treating CT; it wouldn't eradicate CT but only facilitate it to develop silently.
Many countries have legal requirements to report CT as a form of sexually transmitted disease (STD). Patients with CT of the eye such as conjunctivitis or cardiac problems are not required to reveal their sexual partners; physicians wouldn't have reported their CT findings to the Sexually Transmitted Disease Centre. When CT isn't contracted as a form of STD, reporting in this area is totally lacking. This may perhaps be part of the other significant area of concealment of this disease.
C. Theory on Lymphogranuloma Venereum (LGV)
Lymphogranuloma venereum is a sexually transmitted disease caused by CT infection of the LGV strain serotypes L1, L2 and L3. This disease is a representation of CT infection in the lymphatic system. Diagnosis can be made when “closed safety pin” inclusion bodies are seen in the cytoplasm of histiocytes [18]. LGV is primarily an infection of lymphatics and lymph nodes. After CT infection is spread onto the mucosal surface, the organisms seek their way to the draining lymphatics to cause lymphangitis and lymphadenitis. The lymph nodes may become necrotic and results in loculated abscesses, fistulas, and sinus tract, as the acute infection subsides, fibrosis will replace the resultant obliteration of lymphatic drainage, chronic edema, and stricture formation. Leucocytosis usually presents with fever but then it can remain latent for years then develop elephantiasis, strictures and fistulas of the penis, urethra and rectum.
Incubation period of LGV is between 3 to 12 days or longer [9]. It could be a papule, a shallow ulcer or erosion, most commonly a small herpetiform lesion, or non-specific urethritis. The incubation period averages 1 to 3 weeks. In male, it's usually found in the coronal sulcus, prepuce or glans. In women, it's usually found in the posterior wall of the vagina, vulva or cervix.
The secondary stage appears in two main settings. Swelling of the inguinal lymph nodes is the most common presentation men, usually 2 to 6 weeks, after exposure. It can have an incubation period of 10 to 30 days, up to 6 months [9]. The nodes are firm, slightly painful and enlarge over 1 to 2 weeks and are unilateral in two third of the cases. Infected lymph nodes are usually small and stellate. Abscesses are surrounded by histiocytes that coalesce to produce large necrotic suppurative foci. This heals after several months leaving inguinal scars or granulomatous masses of various sizes for life; giving massive pelvic lymphadenopathy [5]. Constitutional symptoms are common and associated with the systemic spread of the disease. However spontaneous recovery occurs in a great majority of the cases. If the femoral and inguinal nodes are involved, it produces the classical "groove sign" at the Poupart’s ligament [9]. In women inguinal lymphadenitis is unusual; however, the iliac lymph nodes may be involved and lead to pelvic adhesions. When this occurs the patient may complain of lower abdominal pain made worse when lying supine. The anorectal syndrome is a more common presentation in women and homosexual male who practise anal intercourse. Rectal mucosa produces granulomas with giant cells, crypts, abscesses and extensive inflammation. Sigmoidoscopic findings may closely resemble Crohn’s disease of the rectum, ulcerative proctitis, proctocolitis with purulent exudates and mucosal bleeding are common. They may complain of anal pruritis, rectal pain and tenesmus. Protoscopic examination may show multiple, discrete superficial ulcerations with irregular borders may appear on the rectal mucosa. Complications include rectal stricture, perirectal abscesses, anal fistula and "lymphorrhoids" which are perianal outgrowths of lymphatic tissue.
Late stage may include genital elephantiasis, genital ulcers and fistulas, urethral and rectal stricture, perineal sinuses, rectovaginal fistulae and frozen pelvis. Chronic LGV in men can progress to infiltrative, ulcerative or fistula lesions of penis, scrotum and elephantiasis if lymphatic obstructions occur. Urethral strictures, usually the posterior urethra, also cause incontinence of urine. The destructive nature of CT is slow and irreversible; nevertheless, if more details of signs and symptoms are made known to the general public, concerted support will increase to facilitate in the eradication of this bacteria.
Diagnosis of LGV is based on both clinical and laboratory investigations which may include the following:
1. Mild leukocytosis with an increase in monocytes and eosinophils.
2. Elevated gamma-globulin concentration due to an increase of IgA, IgG, and IgM [32]. Complement fixation test with titres of 1:64 or greater; however the test may cross-react with other chlamydial antibodies.
3. Microimmunofluorescent test which is diagnostic when the titre is greater or equal to 1:512.
4. Isolation of the organism from bubo pus.
5. Histological identification of chlamydia in infected tissue.
Problem Analysis:
One of the major reasons for long term harbouring of this bacteria is that it isn't being noticed hence spread far and wide can occur without intervention. Better and easier form of detection of this bacteria or even regular screening may help to prevent the spread of CT. Clinical presentations of LGV depend on the sex of the patient, mode of sexual contact, by way of the vagina or anus and the stage of the disease. The primary lesion can be transient and easily missed. Consequently, increase sexual education would certainly empower the sexually active public to be more aware of the need to volunteer for regular screening. However, since CT infections can be spread by other means as well, the general public should learn to be aware of the signs and symptoms of CT infection, to seek medical attention if any significant others in the family are infected.
D. Theory on Elephantiasis
Elephantiasis has various causes and is characterized by the gross enlargement of a limb or areas of the trunk or head. CT infection, hereditary lymphoedema, as well as mosquito’s parasites such as filariasis are some of the common causes of this condition. When lymphatic drainage is blocked an abnormal accumulation of watery fluid in the tissues causing severe swelling occurs. The skin usually develops a thickened, pebbly appearance and may become ulcerated and darkened. Fever, chills and a general feeling of malaise may be present. Elephantiasis may also affect the male and female genital organs. In a male, there may be enlargement of the scrotum, and the penis may be retracted under the skin that has become thickened, non-elastic, hot and painful. The spermatic cords may become thickened. The external parts of the female genital organs, primarily the vulva, may also be affected by elephantiasis. A long, tumorous mass covered by thickened and ulcerated skin may develop between the thighs. There may also be an enlargement of the lymph nodes of the legs.
The extreme enlargement of the limbs and other areas of the body characterized by elephantiasis is the result of obstruction of the lymph flow and possibly of blood circulation. The lymphatic blockage can be due to recurrent attacks of a bacterial infection causing inflammation of the lymphatic vessels, known as streptococcal lymphangitis. If lymphatic obstruction became large, backup pressure in the lymphatic channels cause dilation of the superficial vessels, resulting in extreme swelling. The cycle continues until the affected area is grotesquely enlarged. Death of surrounding tissues may also occur from an obstructed blood supply causing the surrounding tissue to be gangrenous. The traumatized tissue is then vulnerable to streptococcal infection.
Problem Analysis:
Elephantiasis is the evidence of neglect or lack of treatment. This disfiguring consequence occurs as a result of either misdiagnosis or lack of treatment. Organ damage as a result of lymphatic blockage causing elephantiasis is irreversible but again reporting of this condition to health authorities isn't required; perhaps instead of mandatory requirement for reporting of CT as a sexually transmitted disease alone, CT should be reportable as a diagnostic category such as elephantiasis, Reiters Syndrome Arthritis or Cardiovascular CT.
2. New Born CT Infections
Newborns can be infected with CT, presenting as neonatal ophthalmia, before passing through the birth canal or infected during its passage [14]. Dr. Venkatesh M.P. reported that there are case reports documenting CT infection in infants born after cesarean section with ruptured membranes and more rarely, even in those with intact membranes [35]. The latter condition indicates either a transmembrane or a transplacental transmission of the infection [35]. CT infection has been linked with premature delivery resulting from the infection stimulating the rupture of the uterine membranes. Additionally, CT infection can also cause the baby to have low birth weight on parturition. Neonatal infections have been linked to serovar B and D to K [35]. Pregnancy care in many countries includes mandatory testing for sexually transmitted diseases such as syphilis and CT infections. If this regulation were to be made world wide, perhaps control of CT infections would be much better.
It is reported in Harrison’s Principles of Internal Medicine that only 5 to 25% of pregnant women have CT infection of cervix but 50 to 66% of children exposed to CT infected vaginal flora, in the birth canal during delivery, develop CT infection [5]. Careful medical investigations during pregnancy may be the best solution to prevent infection to neonates at birth. Symptoms of an eye infection, conjunctivitis, include discharge in the eye and swollen eyelids and usually develop within the first 10 days of life. Conjunctivitis specimens for culture isolation and non-culture test should be obtained using Dacron-tipped swab on everted eyelid [26]. Performance of this test requires simple skill that can be performed even in primitive settings in under-developed countries hence more frequent screening test should be done as a preventative measure. Testing reveals that only half of infected infants develop inclusion conjunctivitis 5-14 days after birth, 10% may develop pneumonia and some develop otitis media. It is possible that the baby will also develop infections in the anus, genitals and lungs [5]. Symptoms of pneumonia with or without constitutional symptoms, including a cough that gets steadily worse, and congestion, most often develop within 3 to 6 weeks of birth. These symptoms can often be successfully treated with antibiotics. Use of antibiotic ointments or silver nitrate solution drops, effective to prevent gonococcal ophthalmia, is considered ineffective in preventing perinatal transmission of CT infection; however concurrent use of topical ointments with systemic erythromycin antibiotic therapy for conjunctivitis was considered unnecessary [26].
Problem Analysis
Presence of CT in neonates may not be reportable as a sexually transmitted disease. This might be caused by vertical infection or contact with vaginal secretions during birth. Statistics in this area should be considered vital but nevertheless is often ignored.
It has been recommended that all pregnant women be tested for CT infection as part of their prenatal care [31]. The results of such testing must be reported to health care authorities. In Latvia, reporting of disease is mandatory but consequences of non-reporting isn't enforced diligently. The fall through in this area is in the lack of control when prophylactic use of medicine to lower the risk of infections successfully eliminates the accuracy of infection rate hence the tip of iceberg phenomenon is greatly increased.
3. Female CT Infections
A. Theory Pelvic Inflammatory Disease
CT infections in females cause pelvic inflammatory diseases (PID) such as salpingitis, endometritis and ectopic pregnancy [6]. Ectopic pregnancies are common with a significant number of cases, 70000 cases thought to be due to scarring of the tube [5]. Although, Judge RD et al, in his book, Clinical Diagnosis in 1989, proposed that the term, PID, should only be used when caused by gonococcus and streptococcus [16], nevertheless it's now common to include CT infection as the most common cause of PID. Bi-manual examination of a woman infected with CT infection should reveal bilateral adnexal and uterine tenderness, sometimes with guarding similar to appendicitis or pelvic peritonitis, Meckel’s diverticulum and diverticulitis [16]. Tenderness in the cervix, Chandelier’s sign for PID, is often present when conducting a bi-manual examination causing movement of the cervix [14]. The variety of non-specific signs and symptoms makes diagnosing CT infection very difficult hence the vigilance of physicians against CT infection should be increased.
Cervicitis mucopurulent (MPC), caused by CT infection, can be revealed by speculum examination but an increase in neutrophils can be seen in a papsmear. Cervical biopsy will reveal a predominant mononuclear cell infiltrates of the subepithelial stroma with follicular cervicitis [5]. After infection, a painless non-indurated ulcer or papule can appear on the labias, posterior vagina or fourchetter; rarely noticed by women and it heals in a few days without scarring [5]. Vaginal CT infection infections usually spread to inguinal and femoral nodes causing lymphadenitis. If the infection is in the rectum, then hypogastric and deep iliac lymphadenitis are most common. Infected nodes are initially discrete then periadenitis results in matted mass of nodes that becomes fluctuant and suppurative causing the overlying skin to be fixed, inflamed, thin and finally multiple draining fistulas would develop. Extensive enlargement of inguinal nodes around the inguinal ligament, known as the Groove Sign, is considered common but not specific [5].
Problem Analysis:
In females CT infection can be spread, contiguously, by infected secretions travelling along the perineum or via pelvic lymphatics to the anus, causing rectal infections [5]. Although it's usually spread by sexual contacts, CT infection can occasionally be transmitted by fomites or laboratory accidents. Preventative measures such as methodical personal hygiene and observance of obligatory sterile procedures can't be under emphasised in eradication efforts against CT infection. Public education in infection control as well as educating the public about the true nature of CT as a non-sexual disease is equally as important.
B. Theory on Fitz-Hugh-Curtis Syndrome
Curtis, a Chicago gynaecologist, noted in 1930 an association between the presence of "violin string" adhesions between the liver and the abdominal wall and evidence of upper genital tract infection due to gonorrhoea. Subsequently Fitz-Hugh in 1934 described the early manifestations of perihepatitis. It is now known that CT infection is also a contributory cause. Fitz - Hugh - Curtis syndrome (FHC), also known as perihepatitis, due to chlamydiae or gonococci. FHC mostly occurs in women [15]. Upward infections of CT infection transvaginal can also cause salpingitis and endometritis. CT infection infections cause scarring of fallopian tubes hence infertility is a common result. Infertility investigations should consider CT infection as the primary cause despite the lack of overt symptoms. These infections are the results of ascending infection from the lower genital tract to the fallopian tubes; ascending further via paracolic gutters to the subphrenic space, perihepatitis is the result of infecting the liver capsule [37]. It may also involve the spleen, causing perisplenitis, the kidney with renal angle and left upper quadrant symptoms, causing perinephritis or the appendix, causing periappendicitis. Infection may also spread through the blood stream, but rarely, causing perihepatitis; hence perihepatitis in women can be caused via ascending vaginal infection transperitoneally and, although rarely, via the blood stream too. This also may explain why cases of perihepatitis in men are rare [4].
FHC syndrome presents as a sudden onset of frequently severe pain in the right upper quadrant of the abdomen. The pain is typical of peritoneal inflammation, being made worse by movement, deep breathing and abdominal palpation [11]. It may be accompanied by nausea and anorexia. Frequently the pain extends to the back and the right shoulder. There may be right upper quadrant-tenderness; guarding and a hepatic friction rub may also be heard over the right anterior costal margin. Roughly half the patients have low-grade pyrexia, but jaundice and signs of generalized peritonitis are usually absent. However, signs of pelvic peritonitis may be found if carefully sought.
At laparoscopy, "violin-string" adhesions between the liver surface and the abdominal wall can often be visible [34]. These adhesions frequently cause pain. The adhesions are fragile and friable and may be broken at laparoscopy giving the appearance of white fibrous plaques and hemorrhagic spots. The perihepatitis may be associated with ascites, together with the adhesions, may be detectable by ultrasound examination [34]. Thickening of the right anterior extra-renal tissue in perihepatitis has also been observed using ultrasound [30]. Ultrasound can be a useful non-invasive tool to diagnose FHC syndrome or pelvic inflammatory disease [34], [30]. In disease of chlamydial origin, serology may show high levels of antibody to CT [25] however serology alone shouldn't be considered diagnostic.
Perihepatitis can occur with or without clinically evidence of cervicitis or salpingitis; however, they're not mutually exclusive conditions although presence of perihepatitis with salpingitis seems to occur with a higher prevalence of pelvic adhesions [12]. Studies revealed that previous use of oral contraceptive might mitigate occurrence of perihepatitis [22], [36]. Other studies of CT tract infection in female mice suggest that cell mediated immune responses are important for preventing severe upper genital tract infection and perihepatitis [32]. Harrison’s Textbook of Internal Medicine suggested that CT infection antigen with 60KDa heat shock protein maybe the trigger of a pathologic immune response that cause FHCS, tubal infertility and ectopic pregnancy [5].
Problem Analysis
Most commonly patients are initially suspected of suffering from biliary disease. Other possibilities in the differential diagnosis include pleurisy, pneumonia, pulmonary embolism, intra-abdominal perforation. Perihepatitis can occur without liver symptoms [37]. Failure to make the correct diagnosis may lead to extensive and unnecessary investigations and treatment, with neglect of the underlying genital infection. However, careful questioning will elicit a history of genital infection or pelvic inflammatory disease in at least two thirds of patients [4]. Symptoms of tenderness from the right upper abdomen in any woman should be considered a possible indirect sign of a genital infection [37]. CT infection may take many years to be manifested hence post-menopausal or elderly women may possibly suffer from this condition; besides women of any age, even the elderly, can have sexual encounters hence exclusion of CT infection based only on age as a factor or recent sexual contact, in differential diagnosis, would be a mistake.
4. Male CT Infections
Urethritis, Prostatitis, Epididymitis
Urethritis often occurs with prostatitis although they don't necessary occur together; cystitis may also occur as an ascending infection. Digital trans-rectal examination of the prostate can occasionally reveal prostatitis. An inflamed prostate can feel boggy, enlarged or tender on finger palpation. Prostate massage may produce a discharge in chronic prostatitis [27]. Prostate-specific antigen (PSA) and acid phosphatase can be used as a specific marker for differential diagnosis of prostate malignancies [20]. Flu-like symptoms, low backache, swollen-tender prostate, as well as dripping urinary incontinence may be present [18]. Signs are similar in nature to gonorrhoeal infection; in 1786 gonorrhoeal was known as the “dripping disease” [28]. Urinary-tract infections generally produce fever, abdominal or loin tenderness, renal mass, distended bladder, sometimes with enlarged prostate [18]. Ultrasound or cystoscopy can be used to facilitate a diagnosis of inflammation or hypertrophy.
Epididymitis is an inflammation or infection of the epididymis, a convoluted duct that lies on the posterior surface of the testicle. If the inflammation or infection extends to the adjacent testicle, epididymo-orchitis is present. The most common cause of intra-scrotal inflammation is epididymitis. Epididymitis most often, about 50 to 60% of cases, due to the retrograde extension of organisms from the vas deferens and is rarely the result of hematogenous spread.
Coliform bacteria, Escherichia Coli, predominated in infections of prepubertal males. Mycoplasma pneumoniae, enteroviruses and adenoviruses infections are also common in this age group. Sexually transmitted pathogens are the organisms most often responsible for epididymitis in the patient younger than 35 years. Chlamydia trachomatis is the most common while Neisseria gonorrhoeae is the second most common organism responsible for epididymitis. In patients older than 35 years, coliform bacteria predominate because underlying obstructive urinary disease is often present; however, sexually transmitted pathogens can't be excluded.
The progression of epididymitis usually is gradual with symptoms within 24 hours of onset. Initially, the patient may experience abdominal or flank pain because of inflammation in the vas deferens. The inflammation may descend to the lower segment of the epididymis then to the scrotum. Urethritis may accompany a CT infection with the following presentations:
• Scrotal pain and edema
• Urinary frequency, urgency, or dysuria
• Urinary retention from bladder outlet obstruction in older patients
• Nausea
• Fever and chills
• Abdominal or flank pain
• Bilateral epididymal involvement (10%)
• Urethral discharge
• Edematous tender epididymis: Early on, in cases without significant testicular involvement, tenderness may be clearly localized to the epididymis.
• Erythematous edematous scrotum
• Scrotal abscess with fluctuance or fixation to underlying epididymis
• Reactive hydrocele
• Prehn sign is decreased pain with scrotal elevation or support. Prehn sign isn't reliable for distinguishing epididymitis from testicular torsion.
• Urethral discharge (10%)
• Fever or other constitutional symptoms with progression of disease
(Brooks MB, 2005, Section 1 [39b])
Problem Analysis
Signs and symptoms in males are not specific but are nevertheless more easily noticed. Widespread use of screenings or vaccines would help prevent the ongoing spread of disease, especially when males are the main offender in spread of the disease through use of prostitutes or illicit sexual encounters. Most of the vast network of commercial sexual services and sales cater for males. Males are by large the predominant customers; consequently control of STD and CT should be done through education and screened education of male sexual encounters. It can be easily visualised that control of the sexually transmitted form CT through reducing the risk of male propagation would significantly facilitate in community STD control. Australia is one of the countries in which requires prostitutes to have a weekly health certificate in order to work. However, carrying this concept further, perhaps each male client should be required to undertake a quick STD and CT test before being given a health certificate to use prostitutes. The law should make it mandatory that any male found with a prostitute without a health certificate be arrested and jailed.
5. Laboratory Diagnosis
i. Cell Culture Method
This is often considered the most optimal method, the gold standard, of choice for the isolation of CT. However, Harrison’s Principles of Internal Medicine deemed this technique to be less desirable due low and variable sensitivity; it requires good transport conditions, high cost and is technically demanding [5]. This technique takes about 2-3days. It uses cycloheximide treated McCoy cells with one blind passage. The culture can then be stained by iodine, Giemsa reagent or most optimal with specific fluorescein-labelled antibodies to detect CT infection or EB. Thereafter the sample is read under a light or luminescent microscope. Using antibodies with species specificity can enable CT infection species to be adequately distinguished among the three species. Fluorescein-labelled antibodies can also be used to reduce the incubation period but a fluorescent microscope has to be used.
Collection Procedures
In a direct smear, a sample of body fluid is taken from the affected area. In adults, these areas may include the throat, urethra, cervix, rectum, or eye. The skill of person collecting these samples are crucial because it's delicate and difficult to ensure adequate sample collection.
To collect a sample from the urethra or rectum, a swab is inserted into the opening of the urethra or rectum to collect a sample. Pain or discomfort may cause error in inadequate sampling.
To collect a sample from the cervix, a swab will be inserted speculum assisted into the vagina. The speculum gently spreads apart the vaginal walls so the inside of the vagina and the cervix can be examined. Samples are collected from the cervix with a swab or small brush. Experience and skill is crucial in successful collection.
To collect a sample from the eye, a brush will be gently brushed against the insides of the lower and upper eyelids. Flipping the eyelids to collect the samples require experience and skill in this technique of sample collection.
The collected sample will be smeared onto a culture. The culture is infected with the patient’s specimen then centrifuged at 3500 rpm for 60 minutes at 36 degrees centigrade; it's then incubated at this temperature for another 2 hours. Fresh tissue-culture medium containing cycloheximide is added and incubated for 2-3 days. The specimen is then stained with iodine, giemsa reagent or labelled antibody. Finally, the cell monolayer is searched for inclusions and elementary bodies using light or fluorescence microscope, respectively.
ii. Antigen Detection Method
This method is based on direct visualisation of the organism using fluorescein-labelled antibodies specific for chlamydia. Alternatively, detection of chlamydia is based on solubilised component. This method provides standardised technological form with less reliance on technician’s skills and experience as in the Cell Culture Method. Variability and reliability of clinical correlation is better and allows for comparisons of results between laboratories. This detection method is dependent on correct humidity and temperature being maintained; as well, proper collection skills are necessary. Chlamydia being intracellular organisms, in order to obtain sufficient specimen, firm contact with the walls of the canal is necessary for cells collection. This can cause significant discomfort or pain in the penis or cervix hence clinician’s skill of specimen collect is also a major factor to enable accurate results.
Principles and Technique of Direct Antigen Chlamydia trachomatis Test
This chlamydia test involves chemical extraction of its antigen which is a lipopolysaccharide (LPS) followed by a solid phase of immunoassay for the qualitative detection of this extracted LPS. An endo-cervical or penile-specimen is collected by inserting a swab. The extract is added to the sample well with the aid of a transfer pipette and allowed to soak. If CT infection is present in the specimen, it'll react with the conjugate dye, binding to the antibody on the membrane to generate a coloured line in the test window. The presence of two coloured lines, one in the test window, the other in the control window, indicates a positive result. The absence of a line in the test window therefore indicates a negative result. CT infection is an intracellular organism consequently the need to ensure sufficient scraping of cells within the canal can't be over emphasized. The skill of the clinician in the collection of this specimen is important for the success of this technique. This technique has a component of human error but nevertheless is useful because it's simple and convenient.
iii. Direct Fluorescent Antibody Method
This method tests for the presence of CT infection in clinical specimens by labelling it with florescein isothyiocyanate. This allows the direct visualisation of EB in endocervical, urethral, rectal or conjunctival smears. This method is laborious and time consuming but doesn't depend on cold-chain transportation system; hence this isn't storage-time sensitive, when transported from distant clinics. The other advantage of this method is that the clinician can ascertain adequacy of the sample by observing for the presence of cuboidal columnar epithelial cells from the genital tract or conjunctiva. Excessive cervical mucus or presence of predominantly squamous epithelial cells would suggest improper collection and unreliable results.
iv. First Void Urine
First void urine can now be used for testing CT infection hence avoiding the significant discomfort of invasively inserting swaps into the penis. This technique also enables reduction in collection error, although it's nevertheless dependent on the patient’s intelligence and education level for proper first void mid-catch urine collection.
Nucleic acid amplification tests (NAAT). These tests detect the genetic DNA material of chlamydia bacteria. Polymerase chain reaction (PCR) testing is an example of nucleic acid amplification tests. These tests can be done on a urine sample and considered to be more sensitive than conventional cervical smear (www. dynamed.com). Gen-Probe and other DNA probes have been used with similar sensitivity to enzyme immunoassay tests. DNA amplification techniques have enabled increased sensitivity of this technique [33]. It is capable of detecting even one EB. Diagnostic assays using ligase chain reaction (LCR) or polymerase chain reaction have 85% sensitivity from endocervical swab in women and 100% sensitivity from urethral swab in men (www. dynamed.com). However, the drawback in this technique is in contamination both in the clinic and the laboratory. PCR and LCR can be used on urine samples.
LCR is a method of DNA amplification similar to PCR. LCR differs from PCR because it amplifies the probe molecule rather than producing amplicon through polymerization of nucleotides. Two probes are used per each DNA strand and are ligated together to form a single probe. LCR uses both a DNA polymerase enzyme and a DNA ligase enzyme to drive the reaction. Like PCR, LCR requires a thermal cycler to drive the reaction and each cycle results in a doubling of the target nucleic acid molecule. LCR and PCR have comparable specificity (www. dynamed.com).
v. Serology
Serology methods are based on cross reactivity to antibodies produced to CT infection. A variety of serological tests such as complement fixation, agglutination, haemagglutination, immunodiffusion, haemolysis in gel and radioimmune precipitation tests have been used. These tests detect group-specific antibodies but the change in high serological response, to CT infection, has been generally regarded as unreliable because of low sensitivity and specificity for CT infection antibodies detection. Complement fixation test is regarded as insensitive; however, microimmunofluorescence (MIF) is more species and serotype-specific. This test demands high technical skills to detect specific IgG, IgM, and IgA. Consequently, it generally can't be used to specifically diagnose CT infection infections.
However, in Enzyme Immunoassay (EIA) and Indirect Immunofluorescence (IFT) infected cells with one CT infection serotype, purified elementary bodies of CT infection serotype from D to K are used as a single antigen; consequently, differentiation between antibody responses to different serotypes are possible [23]. In contrast, MIF tests detect and separate antibodies to CT infection from different serovars such as non-genital CT infection species to Chlamydia pneumoniae, Chlamydia Psittaci. MIF is regarded as a necessary complement to laparoscopic examination for infertility investigation as a result of CT infection [23]. These techniques are largely automated and lack subjectivity but there's a grey area of reduced sensitivity if likelihood of false positive were to be reduced. Overall, this technique demonstrates high level of sensitivity and specificity compared with Cell Culture Method. Cross-reactivity with other bacteria species may also cause false positive results. Confirmation of results with other technique is recommended.
vi. Surgery/USG
Laparoscopy has been regarded as the Gold Standard to diagnose pelvic inflammatory disease (PID) caused by CT infection [34]. Although this affords limited practical information regarding endotubal morphology, ciliary function or fertility status, nevertheless it provides a clear visual indication of infection. This has to be used in conjunction with other diagnostic methods to confirm CT infection infection. Laparoscopy isn't used as a solitary diagnostic technique, unless there are indications for other collateral procedures, secondary to high cost, and the unnecessary risk of anaesthesia. Other non-invasive procedures such as ultrasound (USG), CT infection and MRI can be useful in facilitating a diagnosis especially in perihepatitis, however, alone they're nevertheless not confirmatory for CT infection.
vii. Diagnosis of CT infection in children for potential criminal investigation
CT infection is often regarded as a sexually transmitted disease hence the diagnosis of preadolescent children with CT infection implies statutory rape that may necessitate, in some countries, a report to be made to the local police for further investigation.
Diagnosis of CT infection among preadolescent children requires high specificity provided by isolation in cell culture that must be confirmed by microscopic identification of intracytoplasmic inclusions, preferably by fluorescein-conjugated monoclonal antibodies specific for CT infection. Although this test has low sensitivity but nevertheless, this is the only test accepted by legal authorities; however, it would be prudent to also perform NAA assay as well [26].
A presumptive diagnosis of chlamydia infection is often made in the syndromes listed when gonococci are not found. A positive test for neisseria gonorrhoea doesn't exclude the involvement of CT infection, which often is present in patients with gonorrhoeal.
Problem Analysis
Diagnostic techniques presently used are often invasive and highly technical, requiring specialized skills and training. Latvia, as well as some other former eastern block countries, is experiencing brain drain to the west; consequently, development of cost effective techniques as well as less skilled labour intensive procedures would greatly facilitate in its prevention programmes. Use of urine samples, instead of urethral swaps, for CT diagnosis is gaining strength in the right direction in reducing sampling trauma to the male patient. Increasing in the speed of processing is equally as important. If it requires few days to one week before test results can be known, perhaps in our present day highly mobile society, the infected patient may no longer be found; also, many more people would have been infected during that wait. Funding and effort should be made in the area of vaccine discovery; in addition, intensive research in the field of early diagnosis, similar to those 5 minutes pregnancy test package, should be made.
6. Treatment Theory
Although CT infection is one of the most prevalent diseases however, its treatment and cure isn't presently difficult but nevertheless scarring and organ damage that has already occurred can't be reversed. There are a variety of treatments available; it ranges from antibiotic use to carrot, celery and beet juice mixed with garlic [13]. However, the most common treatment recommended is the use of one gram of single dose Azithromycin with the advantage in compliance over tetracycline; however, azithromycin’s safety in pregnancy isn't established. If this drug isn't available, some may use 500 mg of tetracycline four times a day for 7 days [7] or a regime of 100mg of doxycycline oral twice a day for 7 days is recommended [38]. Tetracycline isn't recommended for children or pregnant women.
CT infection requires treatment immediately; however, because it frequently occurs with gonorrhoea, presumptive diagnosis and treatment are recommended [3]. It is recommended that during treatment the patient be advised to avoid sexual intercourse as well as alcohol consumption.
Table 3. Conditions that warrant presumptive diagnosis of chlamydia infection [3]:
Condition Chlamydia patients Prevalence in partners
Nongonococcal Urethritis 30-40% 10-43%
Pelvic Inflammatory disease 8-54% 36%
Epididymitis (<35 yo) 50% 10-43%
Gonococcal Infection in Men 5-30% 40%
Gonococcal Infection in Women 25-50% unknown
Table 4. Conditions that may not warrant presumptive diagnosis of chlamydia infection [3]:
Condition Chlamydia patients Prevalence in partners
Mucopurulent cervicitis 9-51% 2-27%
Proctitis (homosexual men) 8-16% Unknown
Acute Urethral Sydnrome 13-63% Unknown
Problem Analysis
When treating any infection with antibiotics, a physician must always balance the possibility of developing resistance patterns against the antibiotic used. Bacterial resistance patterns are based on the minimum inhibitory concentration (MIC) and the minimum bactericidal concentrations (MBC) of an antibiotic against the organism. Gold standard anti-microbial is one that's able to target the pathogenic organism only [24]. Physicians should vary or combine dosages according to different considerations such as patient factors as well as the pharmacokinetics of antibiotic, bacterial profile and its sensitivity pattern. In some societies, compliance to medication dosage isn't always possible; consequently, the use of single dose of oral one gram Azithromycin is most advantageous. Bacteria resistance to existing medication should be the foremost consideration in our combat against CT. Presumptive treatment is an effective way of prevention contingent upon risk of developing resistance to antibiotic. However, cost and affordability of the treatment to local population is an important consideration (39j) especially in countries that don't provide free treatment. Latvia does provide free treatment and follow-up.
CASE STUDY IN LATVIA
On the 16th November, 2007, CDC published an article reporting that CT cases have now surpassed 1030911 cases in the United States. It is now the most ever reported sexually transmitted disease (STD) of any kind (www.uecrescent.org/artilces/stories/public). A case study was conducted in a private urology clinic (shared with other doctors). Urology patients didn't come to the urology clinic for consultation solely because of STD.
Although selection is entirely random but it's nevertheless bias because the presenting population is predominantly male based on natural professional selectivity of urologist. Female patients with CT would usually consult a gynaecologist. Dermatovenerologist as well as general practise physicians would share the load of patients presenting with CT infections.
Patient Profile:
Mr. X who seek medical attention at a private urology clinic. He was born in 1981 hence 26years old. Mr. X was selected because he's the stereotypical patient prototype who attends this urology clinic.
Clinical History: Mr. X was concerned because of complaints of redness and itching on his penis for 2 weeks after intercourse. There was no fever or chills and without pain on urination. There was no discharge reported.
Sexual History: Mr. X had sexual intercourse with a female whom he met for the first time at a club culminating in the present complaint. He denies having a permanent sex partner at home or any previous history of STD despite having had experience with several female partners from the age of 19. Mr. X denies any experience with sexual workers.
Presentation/Examination
There was no redness or rash on the body except a rash on the tip of his penis; about the size of 1 cent coin. No abdominal pain or tenderness or mucopurulent exudates was reported. No lymph enlargement in inguinal, cervical or axila.
Laboratory Diagnosis
Blood test and standard STD test was ordered. The blood test result was normal without rise in white cells or signs of inflammation. VDRL and HIV serology were negative. An endourethral swap was taken for CT test on standard package revealing a positive result from antigen testing for CT and negative for N. Gonorrhoeae.
Diagnosis
Urethritis caused by Chlamydia trachomatis was diagnosed.
Treatment
Doxycycline 100mg orally twice a day for 7 days was prescribed.
Partner Management
Mr. X alleged that he wasn't able to trace his sex partner and didn't have other sex partner during this period.
Discussion Case Study
Mr. X didn't show any previous history of STD within this clinic. However, because national data in Latvia isn't computerised nor shared among health care professionals, the veracity of his statement can't be duly verified. His data could have been duplicated or unreported without any cross reference checking.
This sample patient was selected from three patient data packets at random from the entire urology patient population within the private clinic. Each patient record was examined for the presence of CT laboratory reports. All those patients in each package who has undertaken CT laboratory tests were selected. Sixty six patients were found with CT laboratory reports. Although females were present within this patient population, however, only one female was found in this random sample with this CT test being performed; her result was negative. Sixty five patients were male and six was found to have positive CT test results. Two from these six patients had some STD indications requiring the CT test to be performed. Four others were tested because of other non-STD related, urological conditions but subsequently found to have positive CT results. Six other patients with history of STD were also re-tested for CT but found to be negative.
Comparing this result with the national statistic of Latvia which shows 820 per 100,000 population (0.82%); presently, results obtained in this sample of 66 reveals a prevalence of 6 (9%) with CT infections in this population. This appears to be about 10 times more than the national data presented.
Attending physicians indicated that some of the reason for this disparity is due in part to the fact that this population of urological patients is bias. However, other causes might be due to high usage of antibiotics in the community masking the true figure of CT infections. In addition, different clinics in other locations would present with different infection rates due to presence of “red light” areas within the surroundings of the clinic.
DISCUSSION ON POSSIBLE EPIDEMIOLOGICAL DATA DEFIECIENCIES
I. Some Reasons For The Rest Of The Tip Of Iceberg
1. Lack of Cohesive International Datas. C trachomatis wasn't a notifiable disease until the early 1990s. The situation started to change when first Estonia (1991), Latvia (1992), Russia (1993), Lithuania (1994), Slovenia (1995), and then Hungary (1998) legislated on the notification of C trachomatis. Incidences of chlamydia trachomatis in many European countries were indeed reported to be unknown because it isn't noticeable [8]. Latvia began to collect statistic nationally only in 1992 while data of other sexually transmitted disease were available from as early 1961. Search for comparable data in Eastern European countries on CT reveal no comparative information. Although compulsory reporting is required but in reality it's found to be incomplete or unreliable; for example, Domieka M et al considered inconceivable that, Lithuania, a country with almost four million inhabitants, in 1999, reported 650 cases of CT (39j); however due to different social, legal and economical reasons, data comparison between countries was found to be not feasible. Trachoma caused by CT may in most likelihood not be reported to the authorities as a sexually transmitted disease despite the legal requirement to report chlamydia.
2. Asymptomatic. Chlamydia trachomatis infection doesn't manifest with clearly identifiable signs or symptoms hence identification and diagnosis are extremely difficult. In many instance, it's simply asymptomatic. According to At First Diagnostic, as many as 50% of males and 80% of females are asymptomatic (www.atfirstdiagnostic.co.uk) Symptoms might at times be so mild that patients are not motivated to seek treatment; especially in countries in which free health care are not readily available.
3. Lack of Public Education. Many physicians may not be alerted to the unitary presence of chlamydia with mere constitutional symptoms unless the patient is sufficiently educated to realise and reports that their present constitutional symptoms might be attributed to sexual contacts [19]. In Latvia, it would be socially improper for physicians to probe deeper into sexually practices or related causes if patients unknowingly attribute and insist that the cause of current presenting constitutional symptoms to be due to other non-sexual causes. It would then not be possible for doctors to subsequently test for CT infections especially if urethral swaps have to be taken.
4. In addition, this organism affects multiple organs causing a variety of illnesses; the lack of reporting of the presence of Chlamydia trachomatis in these other systems such as diseases in liver, heart, prostate makes national statistical representation of its prevalence woefully inadequate; even the presence of chlamydia in related conditions such as epididymititis or endometriosis in infertility clinics are not reported to health authorities hence rendering severe national statistical under representation. Presently, physicians are reminded, of the possibility of chlamydia infection, if spot bleeding are detected in women after starting oral contraceptive use [8].
5. Problems with widespread use of antibiotics. The cure of Chlamydia trachomatis, when properly identified, isn't difficult; however, since antibiotics are so frequently used for most common infections or complementary co-infections such as gonorrhoea, the presence of CT infection is easily masked by such partial or ineffective treatment. For example, it's known that about 25% of urethritis patients are infected by double infection of CT infection with gonorrhoea, and if treated with penicilline alone, gonorrhoea is cured but chlamydia remains [8]. Similarly, patient can have a sinus infection or common cold and coincidentally infected by chlamydia through sexual contact; antibiotics treatment for a sinus infection may not eradicate chlamydia hence allowing its spread both within the patient and this may also allow its spread to other sexual contacts. The price and availability of antibiotics were considered to be significant in spread and control of CT (39j).
6. Society Sexual Hang-ups/Embarrassments. This religious and social culture prevents physicians from probing sexual history unless broached by the patient. Latvian society often abhor promiscuous, extra marital or polygamous relationships hence general physicians often don't probe sexual behaviours unless the subject is broached by the patient; otherwise, it's convenient to treat constitutional symptoms symptomatically, generally with short dose of antibiotics, without requiring reference to further laboratory investigation to verify presence of chlamydia or to provide focused antibiotic elimination of this organism. Partial elimination of CT would facilitate its subsequent spread to other internal organs as well as further propagate its survival within the human population by sexual contact.
7. Partner Reporting requirements. CT infection is reported as a sexually transmitted disease. Latvia was the only country reported by Domieka M et al, to have a system of compulsory partner notification and tracing. Latvia began collecting statistical data on CT in 1992 as a form of sexually transmitted disease, however, consistent details has been lacking for any comparative studies to be meaningful. Details in age groups, gender and types of CT infection have not been collected consistently over the years. Latvia has mandatory requirements for partner notification and reporting CT as a sexually transmitted disease but owing to the various non-sexual presentations of CT consequently a large proportion of the data is missed. Enforcement of this regulation is lacking due to absence of a specific punitive action for non-compliance. Estonia has recently enacted financial punitive against physicians for non-compliance (39j). However, legal enforcement may intrinsically be counterproductive because it would force patients to abstain from seeking treatment for fear of revealing their infidelity to their long-term partners. In addition, this would also cause unwilling patients not to remember their sexual contacts. Many CT related conditions are not found in the setting of sexually transmitted disease clinics, for example perihepatitis are usually discovered in gastrointestinal investigations, salpingitis, tubal damage are discovered by gynecologists. The reporting of chlamydia infections to authorities, statistically, doesn't include such conditions as endometritis, PID, salpingitis, sterility or ectopic pregnancy; however, these conditions could also be caused by CT infections. The legal compulsion to report CT infection as a sexually- transmitted disease, may be counter productive in its eradication effort, because it accompanies the patient’s parochial fear of being coerced to require their long term sexual partner to come for treatment. A husband or wife with extra marital affairs or prostitute use would find it difficult to notify their spouse and being subsequently required to account for how they acquired this disease. Failure of partner notification is a major factor in increasing CT infection prevalence causing it to be one of the main sexually transmitted disease; but enforcement of partner notification may also prevent patients from volunteering accurate details of sexual encounters, this would invariably cause misdiagnosis, inappropriate or inadequate treatments; availability of their sexual contacts may in any case not be so readily forthcoming. This is also detrimental in the global aspiration to reduce the prevalence of the disease. Patients with sexually transmitted disease are often treated anonymously hence making enforcement of partner notification purely voluntarily.
8. Moralistic Society and Social Taboos. It must be appreciated that sexually transmitted diseases are regarded as highly sensitive and embarrassing, in this ultra religious, moralistic and puritanical society of holy monogamous relationships, sexual pleasures are regarded as dirty and unbecoming pass times; patients would indeed refrain from seeking treatment if positive identification were to be made compulsory. Children are not able to discuss sexual matters with their parents, especially the illicit kind that causes them to contract transmittable diseases. Children’s knowledge of sexually transmitted diseases is obtained in the back streets or from their equally unknowing peers. Children sex education classes in schools are yet to be accepted in Latvia.
9. Technological Innovations Not Included. When CT infected peritoneal adhesions are identified by laparoscopic techniques, computer scans or magnetic resonance techniques, they're not required by law to be reported to national sexually transmitted disease authorities for accurate representation of CT infections nation or world wide.
Although it's acknowledged that doctors in some countries might report the presence of CT infections based on laboratory reports alone but nevertheless its widespread prevalence is indicative of exponential spread, not represented statistically. It is postulated that the dimension of problems in Latvia caused by CT infection is astronomically underestimated. The dimension and cost of CT infections to society should be emphasized more strongly to prompt a more intensive effort in its elimination. Society should demand urgent attention by healthcare providers as well as national planners to address this problem; perhaps this report will contribute to drawing the much-needed attention for the control or eradication of this organism in saving the woes of mankind and significantly reducing the cost of the healthcare budget.
II. Mode Of Transmission
Chlamydia trachomatis infection is transmitted sexually, in the same manner as Neisseria gonorrheaeae; consequently, many of CT infection’s earlier symptoms could be masked by gonorrheae. Although transmission during vaginal birth, causing neonatal ophthalmia and pneumonia, is also common, however protocol prophylactic systemic treatment of infected mothers and antibiotic eye drops for newborns immediately after birth have reduced or virtually eliminated this mode of transmission manifesting as conjunctivitis or pneumonia in neonates. However, CT infection can be asymptomatic and additionally, it can exist in a carrier state, estimated to be about 10% in adolescents in most societies [8]. Long latency periods or years of sub-symptomatic periods may disguise the presence of the organism. Symptoms may suddenly erupt from an infection contracted many years ago. It is therefore difficult to ascertain whether present condition is due to recent infection or the organism might have been present for a long time. The spread of CT infection has been known to spread among members of the same household [8], the implication is that perhaps, like trachoma, direct contact with body fluids contaminated with infected cells may facilitate the transmission of this disease. It should be recalled that CT infection is an intracellular organism. Although not rigorously investigated or proven, cells infected with CT infection from one host can release RB or EB by extrusion or upon lysis; when transmitted in droplets form, in theory, can spread the disease to the new host in just the same way as body fluids contact during birth infect babies born to mothers infected with CT infection. Oral sexual contacts, anal sex as well as other forms of bodily fluids exchange can similarly transfer infected cells causing spread of CT infection. However, spread of infectious EB from one human to another through means other than sexual contacts such as kissing, blood transfusions or organs transplantations are not established and deserve further research and investigations. In theory, any procedure involving the transfer or exchange of infected cells from one infected individual to another may cause the transmission of CT infection. However, the best-known mode of transmission predominantly is by sexual contact, hence reduction in frequency of multiple sexual contacts, use of condom barrier prophylaxis and proper use of antibiotic prescription and treatments all contribute, presently, to the control of this mode of spread of this organism [10]. Nevertheless, classifying CT as a sexually transmitted disease is intrinsically erroneous and misleading because it ignores other modes of transmission by fomites, flies or social contacts in causing other CT conditions such as trachomas. A substantial number of the eighty-four million infected people, discussed above, may have contracted trachomas through non-sexual contacts.
III. Prevention And Disease Control Formats
Prevention is always the best cure for any disease. However general prevention and control of CT infection is based on STD guidelines because it's predominantly a sexually transmitted disease. Although it's the best format presently available but because CT infections can also be spread by fomites and other social contacts, these preventative measures alone may not be entirely adequate. The five major concepts, recommended by the Centre for Disease Control and Prevention (CDC2006), generally accepted, are:
a) Education and counselling of persons at risk on ways to adopt safer sexual behaviour.
b) Identification of asymptomatically infected persons and of symptomatic persons unlikely to seek diagnostic and treatment services.
c) Effective diagnosis and treatment of infected persons.
d) Evaluation, treatment and counselling of sex partners of persons who are infected.
e) Pre-exposure vaccination of persons at risk for vaccine-preventable STDs.
Although prophylactic use of antibiotic post-exposure to potential infection can be used but there's no acceptable vaccination that can prevent CT infection (39i). Use of prophylactic antibiotic may increase the risk of facilitating the organism’s resistance to effective current antibiotics. If more funding can be made available for research perhaps a vaccine or other more effective preventative method can be developed sooner.
Prevention Methods [3]
1. The most reliable format to prevent sexual exposure to CT infection is abstinence from sexual contact in any form or to restrict oneself to strict long-term monogamous relationship. However throughout the nature of mankind, this hasn't been successful. Prostitution is also known as the world’s oldest profession.
2. Male or Female Condoms when used correctly and consistently are effective in preventing the transmission of CT infection. However, accidental transmission or contact with body fluids on any mucosal surfaces may increase the risk of infection. The use of oil-based lubricants such as body lotions, mineral oil, petroleum jelly or massage oils may weaken the latex. Fingernails, teeth or other sharp objects may also damage the latex condoms causing it to be ineffective in preventing CT infection infections.
3. Vaginal spermicides, sponges and diaphragms including the use of nonoxynol-9 are not effective in preventing CT infection. The frequent use of spermicides containing nonoxynol-9 has been associated with genital lesions rendering an increased risk of disease transmission. Vaginal sponges and diaphragm use has been demonstrated to be effective in protecting women against CT infection; however, no cohort studies have been conducted. Studies have not been conducted in relation to transmission of CT infection to men.
4. Non-barrier contraception, oral contraceptive, intrauterine devices, surgical sterilization and hysterectomy don't offer any protection against CT infection.
5. Partner notification should be encouraged but its effectiveness varies from culture to culture. Mandatory notification can serve as a tool to ensure proper catchments of affected individuals; however, it can also conversely serve as a deterrent, preventing honest declaration of affected partners or prevent infected individuals from coming forward to seek treatment for fear of being forced to disclose their infidelity.
6. Screening tests are recommended for all sexually active and pregnant women on a voluntary basis. 2006 Centre for Disease Control guidelines recommend annual screening for all sexually active women less than 25 years old and for others with new or multiple sexual partners plus retesting women three to four months post CT infection treatment (CDC Sexually Transmitted Diseases Treatment guidelines 2006 PDF) CT infection tests are recommended at the first prenatal visit and third trimester to prevent maternal postnatal complications and neonatal CT infection infections. Screening of women is paramount in preventative measures hence verification of initial positive test should be performed if the test wasn't a positive culture and the patient is considered low risk. However, the candidates with the following profiles are recommended for screening:
• Mucopurulent cervicitis.
• Sexually active women <20 years old.
• Women 20-24 years old who meet the following criteria and those >24 years old who meet both criteria: inconsistent use of barrier contraceptives or new or >1 sex partner in the past 3 months.
• Pregnant females during third trimester.
CONCLUSION
In this modern-day model of medical care, individuals seek medical attention, only when they experience a bothersome sign or symptom; however, at least 50% of individuals infected with CT infection have no sign or symptom. There is public outcry against cardiovascular disease, tuberculosis, and acquired human immunodeficiency virus but the public remains largely ignorant of CT infections. Statistically, the current dimension of CT infection as a problem can be deemed to be grossly under reported; partly because about 50 percent of infected males and 75 percent of infected females have no symptoms; additionally, the current eastern European reporting system and diagnosis of C trachomatis infections remain suboptimal, which allows neither control of the epidemiological situation nor optimal treatment of the patients (39j). The approach to this problem has to be more proactive, reaching out to the population in the form of CT screenings, similar in nature to self-examination breast cancer programs or cervical cancer prevention screening, are necessary. This study has also discussed the various difficulties with screening process. Public education in conjunction with easy access to medical care is paramount for the control of this silent epidemic, the bane of society. Wide availability of prophylactic protection such as condoms and education as to its proper use is a large step towards prevention of CT infection. Screening in democratic society is done voluntarily but involves high cost and availability of medical personnel as well as laboratory resources; consequently the attention of politicians is necessary to accord proper allocation of resources for the funding of preventative screening activities. Public regular screening may be the only weapon against a largely silent disease. However, resolution of partner notification issues in the legal fraternity can curtail the spread of CT infection more effectively. Legal compulsion in partner notification may be counterproductive but conversely slacking in notification allows for the uncontrolled spread of the disease. The balance may lie in the use of social outreach programs such as special teams of communicable disease control personnel performing home visits to conduct education programs as well as collect samples from family members or provide treatment of infected individuals, onsite.
Detection of CT infection in many instances depends primarily upon the vigilance of the medical profession. Until recent years, detection methods have been laborious and traumatic especially for the detection of CT infection in males, when swaps are inserted into the penis causing severe pain; consequently many would opt to ignore the risk of potential CT infection. The availability of using urine samples for the detection of CT infection has greatly facilitated the control of this organism.
Treatment is presently simple but nevertheless early detection is the key to prevention. Scarring, blindness and organ damages that have already occurred can't be reversed despite successful subsequent treatment. The notion is that there are many deficiencies in the present approach to the problem; maybe because the medical fraternity is appeased by the lack of direct mortality figures or the relative ease in which CT can be treated. It might be this ease of achieving a cure that gives complacency hence allowing CT to remain on top of the list of sexually transmitted disease for more than a decade with an ongoing trend of increase every year. However, the present trend should never be allowed to continue.
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39. Internet References
a. www. atfirstdiagnostic.com --- 2007 Chlamydia Labtest.PDF.
b. www. cdc.gov/std/treatment/ -- 2006 CDC Sexually Transmitted Diseases Treatment Guidelines 2006 PDF
c. www. cdc.gov/std/Chlamydia2004/ctsupplement_2004FINAL.pdf
d. www. chlamydia.com
e. www. dynamed.com Chlamydia Genital Infection -- November 11, 2006
f. www. emedicine.com/emerg/topic166.htm -- Brooks MB-- Epididymitis, 2005, Section 1
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h. www. healthlink.mcw.edu -- National Institute of Arthritis and Musculoskeletal and Skin Diseases. National Institutes of Health Article Created: 1999-05-07
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n. www. uecrescent.org/artilces/stories/public
APPENDIX I
Latvian Health Statistics Authority. Data from 1992 to 2006
Syphilis Gonorrhea Neisseria Chlamydia Trachomatis
/100000 Absolute /100000 Absolute /100000 Absolute
2006 20.7 483 32.0 746 35.2 820
2005 19.0 443 29.8 649 31.3 729
2004 25.0 584 23.0 537 22.6 528
2003 33.1 784 20.3 481 21.2 502
2002 28.7 679 23.5 555 24.6 582
2001 25.1 594 23.3 551 24.9 589
2000 43.2 1021 31.5 745 27.3 647
1999 63.2 1541 44.8 1101 29.7 725
1998 105.6 2597 50.3 1237 55.6 1367
1997 121.3 3008 68.1 1690 71.8 1780
1996 124.9 3124 83.9 2099 138.7 3470
1995 91.9 2357 111.2 2853 176.2 4520
1994 59.3 1521 147.1 3774 153.6 3940
1993 31.8 830 162.0 4223 100.8 2626
1992 10.3 273 124.5 3309 31.5 837
Identification
Chlamydia species are readily identified and distinguished from other chlamydial species using DNA-based tests.
Most strains of
C. trachomatis are recognized by
monoclonal antibodies (mAbs) to epitopes in the VS4 region of MOMP. However, these mAbs may also crossreact with the other two Chlamydia species,
Chlamydia suis and
Chlamydia muridarum.
Further Information
Get more info on 'Chlamydia Trachomatis'.
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