Co-infection Chlamydia

There are nine species of the Chlamydia genus known and more are being discovered yearly. Many of these chlamydia are found in water, soil, mammals, reptiles, fish and arthropods including ticks. The role these chlamydia play in human disease remains unknown but they are endemic within various tick species including the ticks that carry Lyme and co-infections. The spread of these chlamydia is not limited to sex, ingestion or inhalation.

Chlamydia are unusual microorganisms.Initially they were believed to be viruses but eventually got classified as gram negative bacteria. Chlamydia are obligate intracellular parasites that use the host resources for their development. Inside cells they extract nutrients to reproduce. They are very good at hiding from the immune system.

Chlamydia trachomatis, c. pneumonia, c. muridarum, c. suis, c. abortus, c. pecorum. c. psittaci, c. felis and c. caviae are the primary chlamydial species. Of these c. trachomatis, c. pneumonia, c. abortus, c. pecorum, c. psittaci and c. felis can infect people. Each Chlamydia species creates numerous serotypes and each serotype causes slightly different disease symptoms. All chlamydia share genetic material with each other. Understanding these organisms is not as simple as physicians would like.

Genetic analysis has found that amoeba-infecting chlamydia are the oldest of the genus, followed by plant-infecting, animal-infecting and the newest being human-infecting species. Chlamydia jumped into people long ago from a domestic animal partner, altering their genome in the process, enabling them to utilize humans as a primary reservoir. Chlamydia are some of the most successful bacteria on earth.

Life cycle

Chlamydia exist in three primary forms:

  • Elemental bodies (EBs): minimally metabolically active extracellular elemental body
  • Reticulate bodies (RBs): highly metabolically active reticulate body
  • Aberrant bodies (ABs): minimally metabolically active aberrant body

The elementary body is the non-replicating infectious particle. The EB is covered by a rigid cell wall. It is responsible for the bacteria’s ability to spread from person to person. Once inside the body it travels to the preferred cellular site, adheres to the host cell, and then alters the cell’s functioning to enable bacterial replication. The EBs generate a vacuole which the host cell ingests.

Once internalized by the cell the EBs shut down the mechanism that the host cell uses to kill invading bacteria. The bacteria then move the vacuole close to the cell’s nucleus and begin stimulating the cell to provide the nutrients they need to reproduce.

Within the infected cell the EB develops into a noninfectious reticulate body. The RB is involved in the replication and growth. It is slightly larger than the EB and does not present a cell wall. The RBs begin dividing. When the vacuole is filled with sufficient organisms the RBs transform back into the EBs. The cell ruptures or the vacuole is extruded out through the cellular membrane. The newly created EBs infect new cells to continue the cycle. Throughout the process the chlamydia modulate the immune system to prevent the immune cells from killing them and to enable the acquisition of nutrients.

The aberrant body is a unique state that allows the bacteria to survive adverse conditions over a long period of time. The bacteria are viable but noninfectious, the metabolism slows and the RB division and differentiation into EBs stops. This state is a form of bacterial hibernation that protects them from environmental impacts that could kill them.

Every chlamydia infects the GI tract. Although they have been found throughout the GI tract they prefer the cecum. They rarely cause disease and infect the outer mucosal layer in a tolerant fashion. This shields them from the effects of antibiotics and gives them protected niche for reproduction. EBs are continually shed in the feces of infected animals. The presence of EBs in feces is a factor in auto inoculation of the vagina and eyes.

Chlamydia trachomatis

Chlamydia trachomatis is the species that causes the sexually transmitted disease. This disease manifests itself in the man as urethritis or in some cases as epididymitis. In women it can cause infection of the cervix or present as urethritis. c. trachomatis is also known as the causative agent of trachoma, a disease of the mucous membrane of the eye and it can cause conjunctivitis.

A special variant of the c. trachomatis bacteria can cause lymphogranuloma venereum. It presents with a sore at the site of infection. This can go unnoticed. After ten to thirty days, inflammation of the lymph nodes will occur, sometimes accompanied by fever.

In newborns it can cause respiratory tract infection and blindness or visual impairment.

Chlamydia pneumonia

Chlamydia pneumonia is primarily a respiratory pathogen infecting lung tissue and bronchi. However the bacteria can disseminate via infected macrophages deeper into lung, arterial and joint tissues. 10% of community acquired pneumonia’s are attributed to c. pneumonia and 50-80% of adults have antibodies against the bacteria.

Generally infections are asymptomatic. Acute infections present as pharyngitis, sinusitis, otitis, bronchitis or pneumonia and can exacerbate asthma, chronic bronchitis and chronic obstructive pulmonary disease (COPD). C. pneumonia can persist for months after initial infection despite antibiotic treatment.

Besides respiratory symptoms c. pneumonia can cause a range of conditions if they migrate into the body. The bacteria can infect the liver, heart, brain, eyes and vascular cells. The primary diseases that occur are of the vascular system and include myocardial infarction, chronic coronary disease, stroke and acute coronary events. Infection with c. pneumonia increases the risk of atherosclerosis.

c. pneumonia is also linked to the development of arthritis and diabetes and similar to C. trachomatis it can infect the nervous system and cause a wide range of moderate to severe neurological problems. The bacteria have been found in the brains of patients with Alzheimer’s and multiple sclerosis.

Chlamydia abortus

Chlamydia abortus is transmitted to people via intake of or contamination by feces, urine and other secretions during close contact with infected animals. Contact with fetuses, placenta and vaginal discharges also spread the infection.

Infection generally presents as malaise, flu-like symptoms, a mild dry cough and can progress to more severe respiratory disease. The infection can be dangerous for pregnant women and cause abortion with severe or fatal complications. These chlamydia organisms can cause arthritis, pneumonia, conjunctivitis and disease of the reproductive organs or nervous system. Just like the other chlamydia.

Chlamydia psittaci

Chlamydia psittaci infects birds. People who come into contact with birds for their profession or hobby run the risk of getting infected. The bacteria shed EBs in fecal matter and despite hand washing can be either ingested or breathed in with secretion aerosols during habitat cleaning. As with other chlamydia, c. psittaci has developed a number of serovars. Each serovar has a slightly different disease presentation and impact.

The bacteria generally infect the lungs and can cause severe respiratory distress with systemic organ involvement leading to serious disease. Autoimmune precursor lesions in Hashimoto’s thyroiditis and Sjörgen syndrome have been found to contain c. psittaci DNA. These organisms are also a source of genital infections, producing similar symptoms as c. trachomatis. Like other chlamydia they can also infect the nervous system.

Chlamydia pecorum

Chlamydia pecorum is transmitted to humans from domestic farm animals. The normal route of infection is by inhalation of bacteria-laden dust that has been contaminated by feces or urine. It causes respiratory infection but the bacteria can also cause abortion, conjunctivitis, encephalomyelitis, enteritis and reactive arthritis. It causes similar diseases a the other chlamydia. C. pecorum is an uncommon source of human infection.

Diagnosis

Diagnosis of chlamydia infection is often difficult when it does not involve the sexual transmitted disease. Despite considerable efforts cure of infection is difficult to diagnose and no accepted serological criteria exist for persistent infection.

The most accurate tests for these organisms are nucleic acid amplification tests (NAAT) of which PCR is an example. Some clinical isolated organisms have become able to delete the target sequence used by diagnostic kits. This can lead to false negatives.

ELISA is a quick test to detect IgA antibodies but is not as sensitive or reliable and can produce much false negatives.

Cell culture is also problematic. It takes 48 hours to grow Chlamydia in the laboratory and when organisms can no longer be cultured from the lungs, pathology persists and the organism can be detected by PCR.

Treatment

For sexually transmitted chlamydia a single dose of 1000mg azithromycin is often curative. When c. trachomatis causes lymphogranuloma venereum antibiotic therapy of 21 days is indicated. However studies find that treatment with doxycycline is more effective than azithromycin.

While there has been concern about chlamydia developing resistance against antibiotics, it has not yet been found in clinical practice.

Chronic chlamydia induced reactive arthritis has been treated in clinical trials with multiple antibiotics. Monotherapy with doxycycline or ciprofloxacin has failed to achieve a clinical cure in these patients. Rifampin in combination with azithromycin or doxycycline may allow for eradication of the organism from persistently infected patients. 6 month combination therapy with rifampin and doxycycline or rifampin and azithromycin resulted in a favorable clinical response.

Clinical trials of antibiotic treatment for Alzheimer’s patients showed mixed results. Treatment with doxycycline and rifampin for 9 months stopped the progression of the neurodegenerative disorder in most of the patients but did not reverse it.

Patients with MS often respond to antibiotics such as doxycycline, azithromycin and rifampin.

The use of betalactam antibiotics may induce the persistent chlamydia AB and exacerbate disease. It is important to keep this in mind when treating tick borne infections in order to minimize the development of persistent forms.

Poly microbial infections

A recent study evaluated the immune response of tick borne disease patients against a wide range of tick borne disease related microbes. Their findings suggest that tick borne diseases do not follow the one microbe one disease theory as 65% of the patients produced immune responses to various microbes.

The German BCA clinic has treated many chronic Lyme patients in Europe and has found a large number of those patients co-infected with chlamydia species. Treating these patients for chlamydia infection improves their symptoms.

It is interesting that clinical trials that evaluate antibiotic treatment for Alzheimer’s and multiple sclerosis report positive effects. Besides chlamydia they find spirochetes and herpes viruses in the brains of patients with Alzheimer’s and multiple sclerosis.

Multiple studies have found chlamydia-like organisms in ticks but it remains unknown what role they play in chronic tick borne disease.

  • Does Lyme disease affect the immune system, causing a latent chlamydia infection to reactivate?
  • Do patients become more susceptible to chlamydia and could it be considered an opportunistic infection that they pick up in the community?
  • Do they contract chlamydia from the tick bite as a co-infection next to Lyme disease?
  • Or can chlamydia be present but do not play a role at all?

These are questions that should be answered and what do we do with severely ill patients in the meanwhile?