BT12 BVM&S AB2 Chlamydia Notes 2024-25 PDF

Lecture title: Chlamydia Lecturer: Professor Gary Entrican Learning Outcomes of the BVM&S AB2 Course Students who pass this course will have knowledge of normal animal structure and function, including immunology and inflammation, and the biology of pathogens (bacteria, parasites and viruses) tha...

Lecture title: Chlamydia Lecturer: Professor Gary Entrican Learning Outcomes of the BVM&S AB2 Course Students who pass this course will have knowledge of normal animal structure and function, including immunology and inflammation, and the biology of pathogens (bacteria, parasites and viruses) that cause disease in animals. Learning Objectives for this lecture on Chlamydia By the end of this lecture students should be able to: Name the species belonging to the genus Chlamydia that have been associated with disease in animals and/or humans Describe the chlamydial developmental cycle Identify the common features of chlamydial infections Give examples of the diseases caused by Chlamydiae in different hosts Explain the difference between protective and sterile immunity and describe how this relates to strategies for preventing and controlling chlamydial infections Chlamydia spp. There are almost twenty species assigned to the genus Chlamydia. Nine of these are associated with major diseases of animals and/or humans. There are at least five other defined species and four further candidate species that have been detected in the eyes, reproductive or gastrointestinal tracts of animals associated with subclinical infections with little or no defined pathology. Two the original genus Chlamydia was sub-divided into two genera in 1999 (Chlamydia and Chlamydophila). The organisms infecting veterinary species were largely (but not exclusively) assigned to Chlamydophila. This classification has now been revised back to the single genus of Chlamydia. Consequently, literature from this period referring to ‘Chlamydophila’ can be read as ‘Chlamydia’. C. trachomatis: human, ocular/urogenital infection, blindness/infertility C. pneumoniae: human, horse, koala, respiratory/multisystem disease C. pecorum: ruminants, pigs, koalas, enteric/multisystem disease C. caviae: guinea pigs, conjunctivitis/pneumonitis C. psittaci: birds, human, respiratory disease C. abortus: sheep, goats, human, abortion C. felis: cats, conjunctivitis/rhinitis C. muridarum: mice, respiratory and urogenital disease C. suis: pigs, pneumonia, enteritis, conjunctivitis Examples of other species are C. avium, C. gallinacean, C. serpentis, C. poikilothermis, C. buteonis, C.crocodili. Examples of Candidatus species are C. corallus, C. sanzinia, C. ibidis, C. testudines. Features of chlamydial infections Diseases caused by chlamydial infections can be persistent or chronic. Re-infections are common and disease is often associated with immunopathology. Infections are treatable with antibiotics. There are no human vaccines, but veterinary vaccines have been licenced for disease prevention in cats and sheep. Chlamydial developmental cycle Elementary Bodies (EB) adhere to the cell membrane, multiple mechanisms involved. Cell entry is by endocytosis, the organisms remain within a vacuole and actively inhibit phagosome-lysosomal fusion. Following transformation of the EBs to Reticulate Bodies (RBs), the RBs divide by binary fission. As the organisms multiply the vacuole expands, becoming visible microscopically and is known as a chlamydial inclusion. Late in the growth cycle there is differentiation and maturation of RBs back to EBs within the inclusion. Mature EBs are then released by extrusion or by lysis of the host cell. Elementary Body (EB): 300-500nm, extracellular infectious stage, non-replicative stage, resistant to environmental stress. Reticulate Body (RB): ~2000nm, non-infectious, intracellular replicative stage, divides by binary fission Elementary Body (EB)  adherence to cell membrane  entry by endocytosis - remains within a vacuole  prevention of phagosome-lysosome fusion  transformation of EB to Reticulate Body (RB)  division - formation of "inclusion"  differentiation to EB  host cell lysis C. trachomatis Genital and ocular serovars, infects human genital tract and conjunctiva. Most common cause of involuntary infertility in women in developed countries and most common cause of preventable blindness globally. Persistent infections and re-infections very common, no vaccine. C. pneumoniae Cause of acute respiratory infections in human, horses, koalas, reptiles and amphibians. Most infections are mild but can cause severe disease. Has a role in chronic inflammatory lung disease and putative links with coronary heart disease. C. muridarum Infects mice, reproductive and respiratory disease, used as a biomedical model for human chlamydial infections. C. caviae Infects guinea pigs, causes conjunctivitis, used as a biomedical model for human chlamydial infections C. suis A very common infection in pigs, associated with conjunctivitis, pneumonia, pericarditis and reproductive disorders and also associated with asymptomatic gastrointestinal infections. C. psittaci Infects parrots, game birds, pigeons and poultry. Clinical signs primarily manifest as diarrhoea, anorexia, respiratory distress, sinusitis, rhinitis and conjunctivitis. Is zoonotic, in humans is associated with respiratory infections - psittacosis (psittacines) & ornithosis (other birds). C. felis Causes conjunctivitis and rhinitis in cats, evidence of zoonotic transmission but this is rare. Commercial vaccine available. C. pecorum A common pathogen of ruminants, pigs, koalas and other marsupials. Causes enteritis, conjunctivitis, pneumonia, polyarthritis, encephalomyelitis, metritis and mastitis. The most common chlamydial infection in sheep and can complicate EAE diagnosis caused by C. abortus (see below). In koalas causes keratoconjunctivitis (blindness), urinary/genital tract infections and infertility. Great interest in developing a vaccine for koalas, a vaccine trial in wild koalas began in March 2023. C. abortus Causes Ovine Enzootic Abortion (OEA)/Enzootic Abortion of Ewes (EAE). Is the leading diagnosed cause of abortion in sheep (ahead of Toxoplasma gondii, Campylobacter and Salmonella and Listeria). C. abortus usually causes late abortions or stillbirths (also weak offspring). Fetus can be infected but is not usually necrotic. There is distinctive placentitis with thickened placental membranes covered with exudate. If ewes contract C. abortus during early gestation, they abort late in that gestation. If ewes contract C. abortus when not pregnant they can develop a persistent subclinical infection and abort towards the end of their next pregnancy. Ewes seldom abort from EAE more than once. C. abortus is very dangerous zoonotic pathogen that can be fatal for pregnant women. Unlike in sheep, this is an acute infection in humans and there is no evidence of persistence. Although a EAE is a reproductive disease, infection is by ingestion/inhalation, sexual transmission is not a major route. The site of latent/persistent infection in non-pregnant sheep is unknown. Commercial vaccines are available, there are concerns regarding the safety of the live vaccine due to associations with abortion, hence the need for an improved vaccine. Barriers to management and control of OEA/EAE Good vaccines, diagnostics and biosecurity measures can reduce the risk of EAE. Current knowledge of how existing vaccines work and why they might fail is very poor from an immunological perspective, hence the need for new vaccines. Vaccines and diagnostics go together as control measures. It is very difficult to diagnose persistently infected sheep with current tests, as is the ability to differentiate between infected and vaccinated animals (DIVA), which is important due to the possibility of subclinical persistent infections that may lead to future disease and transmission to other susceptible animals. Primary infection in non-pregnant small ruminants often leads to subclinical persistence, indicating that the immune response controls the infection does not eradicate the organism. The inability of the host immune response to eradicate the pathogen after primary infection indicates that sterile immunity* is not induced at this stage. However, after abortion in one season, repeat abortions in subsequent seasons are rare, indicating the induction of protective immunity** following abortion. Despite protection against disease, this may not be sterile immunity as there is evidence of shedding of organisms at oestrus in some sheep that have aborted previously. Protective immunity is sufficient to prevent disease in the infected host, but may not stop transmission of the infection from one host to another. Knowledge of the health history of ewes is therefore important when buying replacements for breeding flocks. *Sterile immunity means that the host immune response eradicates the infectious agent from the body and resistant to future infection. **Protective immunity means that the host immune response prevents disease occurring, but the infectious agent may not be eradicated and/or the host may be susceptible to re-infection, which could lead to further spread. Induction of sterile immunity is therefore a desirable goal for vaccination but may be difficult to achieve. Solutions We require a better understanding of host-pathogen interactions to explain how persistence is established, where persistence is established outwith pregnancy, and why protective immunity usually only occurs after abortion. This knowledge will underpin research into better diagnostic tests and subunit vaccines.