10-Rare Bacterial Infections (1).pdf

Rare Bacterial Food-Borne Infections Brucella spp. Brucella spp. Brucellosis is an acute or chronic infection caused by Gram-negative bacteria from the genus Brucella Human infections are also called Bang’s Disease (B. abortus) or Maltese fever (B. melitensis) Brucellae are coccoid to short rods, no...

Rare Bacterial Food-Borne Infections Brucella spp. Brucella spp. Brucellosis is an acute or chronic infection caused by Gram-negative bacteria from the genus Brucella Human infections are also called Bang’s Disease (B. abortus) or Maltese fever (B. melitensis) Brucellae are coccoid to short rods, non-motile, obligately parasitic, and only have a moderate ability to survive outside of a host They are very important human and veterinary pathogens – it is one of the world’s most common zoonotic pathogens They cause abortion and infertility in foodproducing animals – thus cause economic hardships in areas where the disease has not been controlled Agents infecting humans include B. abortus (main host is cattle), B. melitensis (sheep, goats, camels), B. suis (pigs, reindeer, wild boar, hare, and cattle), and occasionally B. canis (dog) Roop et al., 2021. Uncovering the Hidden Credentials of Brucella Virulence. MMBR 85(1) Brucella sp. Brucellosis in humans is closely related to spread of Brucella in farm animals and correlates with how much it has been controlled People at particular risk are those in contact with animals such as veterinarians, farmers, ranchers, those handling artificial insemination, abattoir and slaughterhouse workers, hunters, and those handling raw milk in endemic areas Australia, Canada, New Zealand, and Western Europe have eradicated brucellosis from their livestock – the USA is also nearing eradication Canada was declared free of the disease in 1985 – the last known infection was identified in livestock in Saskatchewan in 1989 Canada has two wildlife reservoirs of brucellosis: Bovine brucellosis is present in free ranging bison herds in around Wood Buffalo National Park, with straddles the border between Alberta and the Northwest Territories Rangiferine brucellosis is present in free-roaming caribou and reindeer in the arctic and sub-arctic Canada has extensive management plans to prevent the spread of brucellosis from wildlife populations to domestic livestock Transmission and Spread in Animals Roop et al., 2021. Uncovering the Hidden Credentials of Brucella Virulence. MMBR 85(1) Transmission and Spread in Animals Animals can be infected with brucellosis: Through direct contact with infected tissues or fluids from an infected animal By consuming colostrum or milk from an infected animal By consuming feed or water that has been contaminate with infected tissues or fluids Following infection, the bacteria spread through the blood and lymphatic system and infects the reproductive organs, mammary glands, and joints. This can cause abortions, weakened offspring, and lasting infertility In cattle, abortions are the main clinical sign. Most animals abort during the first pregnancy following infection – but will carry subsequent pregnancies to term – but they remain carriers of the infection for life, and will continue to shed large quantities of the bacteria during following births and in their milk Infected males develop testicular infections that reduce their fertility Some infected animals develop joint infections that result in lameness and reduced fertility Treatment or Vaccines for Animals Treatment of infected livestock does not eliminate the infection since intracellular bacteria can persist in lymph nodes and other organs Treatment requires long courses of antibiotics and may only achieve remission – not elimination of the infections Vaccines have been developed to prevent symptoms – but do not successfully prevent animals from becoming infected. Vaccines make serological testing results irrelevant, so vaccination is not permitted in most countries that have declared eradication Vaccination of cattle for brucellosis is not permitted in Canada If brucellosis is detected in livestock in Canada – CFIA immediately humanely destroys and disposes of all infected animals and all animals exposed to the infection (compensation is paid for animals that the CIFA orders be destroyed) In Europe, scientists are not allowed to do live animal experiments with Brucellosis Summary of Brucella transmission in animals Brucella spp. cannot survive long in the environment Brucella spp. is highly infectious – and is very host specific Brucella spp. is a chronic infection, which is usually lifelong due to the remarkable ability of the bacteria to survive and persist in macrophages Animal to animal transmission via exposure to aborted fetuses, vaginal secretions, in utero or via consumption of contaminated milk is common Humans are an incidental host and human-to-human transmission is extremely rare Human Transmission and Symptoms Infection generally occurs due to exposure to secretions of infected animals Consumption of raw milk or meat is another pathway – including raw milk cheeses Sexual transmission between humans is theoretically possible, but is very rare, if it occurs The incubation period in humans is 1-3 weeks, but can be up to three months In humans the symptoms include headache, backache, depression, fever, sweats, and anorexia As the disease progresses humans experience gastrointestinal symptoms, abdominal pain, nausea, vomiting, hepatitis, diarrhea, and possible constipation. In 20-60% percent of cases the musculoskeletal system is affected with humans experiencing spondylitis and arthritis, 5% of cases will develop meningoencephalitis, 2% will experience endo- or pericarditis. B. melitensis will also cause undulating fever For treatment at least two antibiotics are prescribed for 6 weeks – but relapse is common For patients with brain or bone involvement, antibiotics are prescribed for 3-6 months, and for patients with endocarditis antibiotics are prescribed for > 6 months. Bauderfeind et al., Zoonoses. John Wiley & Sons, LTD. 2015 Brucella spp. Virulence Factors Roop et al., 2021. Uncovering the Hidden Credentials of Brucella Virulence. MMBR 85(1) Brucella spp. Virulence Factors The Type IV Secretion System (T4SS) is the most well-known virulence determinant in Brucella spp. The T4SS is conserved across all Brucella species, and deletion knockout mutants are highly attenuated in mammalian cells, and in experimental hosts Since Brucella is predominantly intracellular in mammalian hosts, the function of the T4SS is to control intracellular trafficking of Brucella containing vacuoles in host macrophages so that the bacteria can avoid being killed in phagolysosomes In host cells Brucella lives in acidified phagosomal compartments known as endosomal Brucella-containing vacuoles (eBCVs) There is no replication in eBCVs, but the acidity signals the induction of genes that express the T4SS T4SS effectors are secreted into the host cell that redirects intracellular trafficking Brucella spp. Virulence Factors The effectors initiate extensive interactions with the host cell endoplasmic reticulum (ER) This leads to the formation of replicative BCVs (rBCVs) rBCVs are only slightly acidic, and where intracellular Brucella sustains chronic intracellular persistence in the host Eventually rBCVs interact with the host cell’s autophage pathway and result in the formation of autophagic BCVs (aBCVs), which are thought to be important for bacterial egress and cell-to-cell spread in the host. Brucella T4SS Effectors Brucella Immunosuppression Brucella is also very good at modulating the host immune response The T4SS effector VceC interacts with the ER chaperone BiP This causes ER stress and induces the unfolded protein response (UPR) in infected cells This stimulates the production of interleukin 6 (inflammatory cytokine), and tumor necrosis factor Production of inflammatory cytokines by macrophages leads to granuloma formation – which further facilitates chronic infection Granuloma formation A granuloma is a compact immunological structure rich with macrophages at the center Macrophages can undergo specialized transformation into other cell types A lymphocytic cuff that is made of B and T cells characterizes the periphery of the granuloma The structure is also composed of neutrophils, dendritic cells, natural killer (NK) cells, and fibroblasts Ndlovu et al., 2016. Granulomas and Inflammation: Host-Directed Therapies for Tuberculosis. Front Immuno. (7) 10.3389 Brucella Immunosuppression VceC-mediated inflammatory cytokine production by placental trophoblasts also leads to host cell death and fetal death Thus, the VceC effector may also play an important role in transmission The T4SS effectors BtpA and BtpB inhibit inflammation and cytokine production by dendritic cells The ability of T4SS effectors to both over stimulate and suppress the host immune response is what likely allows the bacteria to stimulate enough of a response to benefit their long-term intracellular survival, but not to elicit a strong enough response to result in sterilizing immunity and infection clearance. Lipopolysaccharide Most Brucella strains produce an LPS molecule, almost all Brucella have a polysaccharide O-chain, core, and lipid A B. ovis and B. canis do not have an O-chain The O-chain protects Brucella from the bactericidal activities of the complement and antimicrobial peptides in phagocytes O-chains also facilitate entry into host cells by allowing the bacterial to interact with mammalian lipid rafts and stimulating the endocytic pathway This is the first step of the formation of the rBCV O-chains also play an important role in immune evasion because the endocytic pathway does not stimulate proinflammatory cytokine production in macrophages and dendritic cells The Lipid A (which is the endotoxin component of LPS) of Brucella also does not induce strong inflammatory responses This is complicated, but is because long chain fatty acids found in Brucella Lipid A prevent interactions with Toll-like receptors Dendritic Cells Roop et al., 2021. Uncovering the Hidden Credentials of Brucella Virulence. MMBR 85(1) Dendritic Cells Dendritic cells (aka antigen-presenting cells) are a heterogenous family of immune cells that are an important link between innate and adaptive immunity The main function of dendritic cells is to capture, process, and present antigens to adaptive immune cells (B and T cells) Dendritic cells will produce cytokines to call immune cells to call and direct T cells Brucella produces a number of outer membrane proteins (OMPs) that block dendritic cells from activating inflammatory cytokine production Omp25 inhibits dendritic cells from maturing, and immature dendritic cells can’t produce cytokines Omp19 has strong immunomodulatory activities by blocking Toll-like receptor 2 It can also induce immunopathology in the bone and central nervous system BtpA and BtpB are T4SS effectors that block cytokine production Cyclic B Glucan (CBG) prevents BCVs from fusing with lysosomes and degrading the cells CBGs also block the ability of dendritic cells to produce cytokines Prevention Consumption of unpasteurized milk and milk products from endemic areas should be avoided People working with potentially infected animals should wear gloves and facemasks Infected mothers should not breast feed – or should heat milk before feeding Bacillus anthracis Bacillus anthracis Bacillus anthracis is the causative agent of anthrax It is nonmotile, spore forming, Gram-positive rod The vegetative form is found in the host, outside the host it forms a spore that is resistant to environmental changes such as desiccation, heat, cold, and UV light B. anthracis can remain infectious in soil for decades It occurs world-wide and is endemic or sporadic in countries with insufficient veterinary services (Central and South America, Asia, Africa, and the Middle East) Spore arise under natural conditions – mainly via degradation of infected carcasses. Animals (especially ruminants) become infected via grazing Transmission to Humans Humans are primarily infected though contact with infected animals and their products The most frequent transmission is via skin abrasions, injuries, and small blemishes. Airborne transmission can occur via sheep shearing or work in tanneries Consumption of meat or raw milk from infected animals may also lead to infection and severe illneses Anthrax There are three types of anthrax infections that can occur in humans: Cutaneous anthrax – most common, occurs through breaks in the skin, and causes coal-like skin lesions Pulmonary anthrax – rare, occurs from inhaling airborne spores. Symptoms resemble the common cold but progress to severe breathing problems and shock Gastrointestinal anthrax – contracted from eating contaminate meat or milk from an animal with anthrax. Causes fever, vomiting, diarrhea, weakness, and other GI problems. On autopsy there are necrotic areas in the intestinal tract In Canada anthrax cases have occurred from Alberta to Ontario – there have been repeated outbreaks in the Mackenzie Bison Range in the Northwest Territories and in Wood Buffalo National Park in northern Alberta There have been no cases of pulmonary or gastrointestinal anthrax in humans in Canada Anthrax fatalities Untreated cutaneous anthrax has a case-fatality of 10-40% (the later if septicemia or meningitis develop) The case-fatality of pulmonary or intestinal anthrax is 90-100% without early treatment Prevention Controlling anthrax in animals is the best way to prevent human infections This includes early recognition, culling, or closing entire stables or farms For exposure, prophylaxis via antibiotics or vaccination and antibiotics is recommended In the USA (in endemic areas) a vaccine that is produced from culture filtrates of toxigenic B. anthracis is available for humans and animals Human vaccination is restricted to high-risk people such as laboratory or military personnel Tularemia Francisella tularensis Francisella tularensis is a Gram-negative, aerobic, non-motile coccoid to pleomorphic (can come in many shapes and sizes) rod F. tularensis is known to infect more than 125 animal species worldwide In humans it may remain asymptomatic, or symptoms can range from skin ulcers to severe typhoid-like generalized illness F. tularensis is an obligate parasite, but in endemic areas it can be found in surface waters and water sediments Some isolates can multiply in aquatic protozoa In vertebrates F. tularensis is a facultative intracellular parasite Global Distribution and Human Infections It is endemic in USA, Russia, Scandinavia, Czech Republic, Slovakia, Austria, Switzerland, and Germany. In Europe it occurs in all countries except UK, Iceland, and Portugal In Canada is can infect rodents, rabbits, muskrats, and beavers Cases occur sporadically in humans, but outbreaks of >100 people have been documented It is a risk for hunters, taxidermists, cooks, and people working with wild-game or in laboratories Infection occurs via: Direct contact with feces, blood, or organs of infected animals - can enter via cuts on the skin or via eyes Bites from cats or squirrels Ingestion of undercooked contaminated meat (wild-game has higher recommended cooking temperatures in Canada) Safe Cooking Temperatures https://www.canada.ca/en/health-canada/services/general-food-safety-tips/safe-internal-cooking-temperatures.html Streptococcus pyogenes Sp has been isolated from lactating cows with mastitis Sp is Gram-positive and has been associated with human pharyngitis and with sore throats, fever, chills, and weakness. In some cases, nausea, vomiting, and diarrhea can be present Food-borne Sp results from the consumption of raw milk Control measures include milk pasteurization, and people who are suffering from an identified Streptococcus infection should not handle ready-to-eat foods. Coxiella burnetii Coxiella burnetii causes Q fever in humans Food-producing animals can carry Cb without symptoms People handling animals, raw milk, and meat can be infected and develop Q fever Symptoms include fever, malaise, anorexia, muscular pain, and headache Symptoms appear 2-4 weeks after infection Infection from consuming raw milk is also possible Cb is the most heat resistant bacteria found in raw milk Cb is killed by pasteurization, but time /temperature must be higher because of this organism It required 62.8∘C for 30 minutes, or 71.1∘C for 15 seconds. Q fever is not nationally notifiable. Anecdotal reporting has been published with the most recent report of Q fever from Newfoundland in the spring of 1999. Abortions in goats were associated with an illness in goat workers at a farm in rural Newfoundland. A serologic survey of 66 individuals indicated recent infection in 37% of these workers. Independent risk factors included contact with goat placenta, smoking tobacco, and eating cheese from pasteurized goat milk. No previous cases of Q fever had been reported in Newfoundland. From 1993 to 2001, a total of 11 cases of Q fever have been reported in Alberta; eight males and three females. Six cases were reported in 2002; four males and two females. From 1993 to 2004, more than half of the reported cases occurred in 25 – 59 year olds. The majority of cases indicated an unknown source of infection, the remainder report contact with animals on farms in Alberta (goats and sheep). Three cases were reported in 2003 and four cases in 2004.