Lec. 5 Systemic 2025 PDF

Non-Enterobacteriaceae affecting GIT 2- Vibrio ❖ They are Gram-negative, comma-shaped, motile with a single polar flagellum (darting motility). ❖ facultative anaerobes which are oxidase-positive. ❖ Vibrio cholerae, the causative agent of cholera. ❖ Vibrio cholerae is t...

Non-Enterobacteriaceae affecting GIT 2- Vibrio ❖ They are Gram-negative, comma-shaped, motile with a single polar flagellum (darting motility). ❖ facultative anaerobes which are oxidase-positive. ❖ Vibrio cholerae, the causative agent of cholera. ❖ Vibrio cholerae is thus transmitted by drinking contaminated water. ❖ It survives in fresh water and, like other vibrios, in salt water. ❖ Food is another means of transmission. ❖ In Asian countries like Japan, it is transmitted through the ingestion of sushi and sashimi. Clinical significance of Vibrio cholerae (Cholera) Profuse watery diarrhea, sometimes described as (rice-water stools), vomiting, rapid heart rate, loss of skin elasticity, dry mucous membranes, low blood pressure, thirst, muscle cramps, and restlessness or irritability. Complications include acute renal failure, severe electrolyte imbalances, and coma. If untreated, severe dehydration can rapidly lead to shock and death. Choleragen (cholera toxin), composed of A B subunits that lead to activation of adenylate cyclase activity, then increased intracellular cAMP and efflux of CL− and leads to secretion of H2O, Na+, K+, and HCO3− into the intestinal lumen and profuse watery diarrhea. Diagnosis: Grow on alkaline peptone (PH 8-9) forming a surface pellicle within 8 hours. Selective medium is Thiosulfate Citrate Bile Sucrose (TCBS) agar yellow colonies. Microscopy, serological, and PCR. Treatment: Oral or intravenous hydration is the mainstay of cholera treatment. Doxycycline is recommended as first-line treatment for adults, while azithromycin is recommended as first-line treatment for children and pregnant women. Vaccination: (koll’s vaccine is an oral vaccine that combines purified B subunit + killed whole cells). A live attenuated oral vaccine prepared by the recombinant DNA technique. Note: Vibrio parahemolyticus or Vibrio vulnificus (halophilic marine organisms) also cause severe GIT manifestations and wound infections.  1- Pseudomonas aeruginosa Non-Enteric 2- Haemophilus Gram-negative 3- Bordetella rods 4- Brucella 5- Legionella 6- Bacteriod  1- Pseudomonas aeruginosa Pseudomonas aeruginosa is a free-living bacterium, facultative anaerobe, commonly found in soil and water. It is an opportunistic and primarily nosocomial pathogen. Characteristics: ❑ Pseudomonas aeruginosa is a Gram-negative rod, motile using a single polar flagellum. It has very simple nutritional requirements. It is often observed "growing in distilled water", which is evidence of its minimal nutritional needs. ❑ Its optimum temperature for growth is 37 ℃, and it can grow at temperatures as high as 42 ℃. ❑ It is resistant to high concentrations of salts and dyes, weak antiseptics, and many commonly used antibiotics and might be found in biofilm, attached to surfaces. ❑ P. aeruginosa typically produces a blue-green pigment called pyocyanin. Virulence Factors of Pseudomonas aeruginosa: A) Adhesins: 1- The fimbriae of Pseudomonas will adhere to the epithelial cells of the upper respiratory tract and other epithelial cells as well. 2- Mucoid exopolysaccharide (referred to as alginate slime) attaches to the tracheobronchial mucin also it protects the bacteria from lymphocytes, phagocytes, and the ciliary action of the respiratory tract. B) Siderophores: (Iron-chelating growth promoter). ❑ pyochelin & pyoverdine are siderophores that accumulate iron. ❑ Iron is necessary for the growth of all bacterial species and affects P. aeruginosa pathogenesis. ❑ Pyoverdine is the main siderophore of P. aeruginosa. C) Type III secretion system (TTSS) D) Toxins and extracellular products that promote local invasion and dissemination of the organism: Cytotoxin Elastase enzyme Alkaline protease Exotxin A has the same mechanism as diphtheria toxin. Hemolysins LPS Clinical significance: 1- Respiratory Infections: Pneumonia: Bacteremic pneumonia commonly occurs in cancer patients undergoing chemotherapy. 2- Central Nervous System Infections: P. aeruginosa causes meningitis and brain abscesses. ❖ Portal of Entry: Inner ear or paranasal sinus - Inoculated direct Surgery: Spreads from another site of infection like the urinary tract. 3- Ear infections "swimmer's ear" : The bacterium is infrequently found in the normal ear, but often inhabits the external auditory canal in association with injury, maceration, inflammation, or simply wet and humid conditions. Lower respiratory tract colonization of cystic fibrosis patients. 4- Eye infections: It is one of the most common causes of bacterial keratitis and has been isolated as the etiologic agent of neonatal ophthalmia in newborn infants. Pseudomonas can colonize the ocular epithelium using a fimbrial attachment to sialic acid receptors. If the defenses of the environment are compromised in any way the bacterium can proliferate rapidly and, through the production of enzymes such as elastase, alkaline protease, and exotoxin A, cause a rapidly destructive infection that can lead to loss of the entire eye. 5- Urinary tract infections Usually hospital-acquired and related to urinary tract catheterization, instrumentation, or surgery. ❖ Third leading cause of hospital-acquired UTIs. Pseudomonas can invade the bloodstream from the UT. Diagnosis: 1) Culture characteristics: a- On MacConkey’s medium: Pale yellow colonies (non-lactose fermenter). b- On nutrient agar: Pseudomonas has a characteristic aromatic grape-like sweetish odor and forms greenish blue colonies on agar at 37°C after 24 hr due to produce two types of pigments; pyocyanin (bluish green) and fluorescin (yellowish gray). c- Selective media: cetrimide agar 2) Biochemical reactions: Oxidase test may be performed in suspected non-pigmented strains Non sugar fermenter. Positive oxidase reaction. Fluorescence under ultraviolet light is helpful in early identification of P. aeruginosa colonies in wounds. 3) Typing: Typing is performed for epidemiological purposes by: A. phenotyping: Phage typing. Bacteriocin typing; produces pyocin. Serotyping according to O antigen. B. Genotyping: rRNA homology. Plasmid profile analysis. Treatment: It has rapid development of resistance mutations and mechanisms of antibiotic resistance. Pseudomonas infections typically occur in patients with impaired defenses. Aminoglycosides, β-lactam, and quinolone.  2- Haemophilus Haemophilus influenzae, is the major human pathogen of this genus. Pleomorphic in shape, ranging from small coccobacilli to long. H. influenzae is a fastidious organism, that requires supplementation with hemin (X factor), and Nicotinamide Adenine Dinucleotide (NAD+) (V factor). It is a normal component of the upper respiratory tract flora in humans and may also colonize the conjunctiva and genital tract. H. influenzae may be: a) Capsulated (typable): produce a capsule. Serious, invasive H. influenzae disease is associated particularly with capsular type b (Hib). Hib is especially important as a pathogen for young children, although it can cause disease in adults. b) Non-capsulated (Non-typable): may also cause serious disease and is a significant cause of pneumonia among older adults and individuals with chronic lung disease. Clinical significance: H. influenzae is transmitted by respiratory droplets. ❑The capsule is antiphagocytic and facilitates hematogenous dissemination. ❑A protease produced by the organism degrades secretory IgA, facilitating colonization of the upper respiratory tract mucosa. ❑H. influenzae can enter the bloodstream and disseminate (Bactereamia). ❑H. influenzae is a leading cause of bacterial meningitis, primarily in infants and very young children, frequently in conjunction with an episode of otitis media. ❑ Mortality from meningitis is high in untreated patients. It is also responsible for the secondary bacterial infection that occurs after influenza virus infection. Diagnosis: - Fastidious microorganism cultured on chocolate agar. - Capsular swelling (quellung) reaction. - Latex agglutination test for detection of capsular antigen. Treatment: ❖ Respiratory infections and otitis media can be treated using trimethoprim-sulfamethoxazole or Ampicillin/clavulanate. ❖ Meningitis, epiglottitis, and other life-threatening illnesses can be treated using ceftriaxone or cefotaxime.  3- Bordetella The human pathogens of this genus are: Bordetella pertussis causes pertussis (whooping cough), and Bordetella parapertussis causes a mild pertussis-like illness. Aerobic, small, encapsulated coccobacilli, grow singly or in pairs. The mode of transmission of Bordetella is via droplets spread by coughing. Pathogenesis: Fimbriae and Filamentous hemagglutinin (FHA): for adhesion. Pertussis toxin: Lymphocytosis, sensitization to histamine, activation of insulin production resulting in hypoglycemia. Tracheal cytotoxin: Inhibits cilia movement and regeneration of damaged cells. Adenylyl cyclase toxin: Decreased chemotaxis and phagocytosis of bacteria. Dermonecrotic toxin: Causes vasoconstriction and ischemic necrosis. Clinical significance: - Pertussis is a highly contagious disease and a significant cause of morbidity and mortality worldwide. - In some countries, this disease is called the 100 days' cough or cough of 100 days. - Disease is generally most severe in infants. But it can be milder in persons have been vaccinated with a pertussis vaccine. Pertussis has three symptomatic stages: 1. Catarrhal phase: begins with relatively nonspecific symptoms (rhinorrhea, mild conjunctival infection, malaise, and/or mild fever) and progresses to include a dry, nonproductive cough. Patients in this phase of the disease are highly contagious. 2. Paroxysmal phase: paroxysms of Uncontrollable-coughing followed by a “whoop” (as a high-pitched intake of breath after cough). Large amounts of mucus are produced. Leukocytosis and cyanosis and/or end with vomiting are very characteristic. 3. Convalescent phase: requires at least an additional 3 to 4 weeks. The patient is susceptible to secondary infections (otitis media and pneumonia). Laboratory identification: - Culture of B. pertussis on Bordet- Gengou or Regan-Lowe media (selective and enrichment media). - Serologically or PCR. Treatment: Erythromycin is the drug of choice. Trimethoprim-sulfamethoxazole is an alternative.  4- Brucella Brucella is primarily pathogenic to particular animal species. Brucella abortus (cattle) Brucella melitensis (goats and sheep) Brucella suis (swine) Brucella canis (dogs) Brucella is an aerobic, facultative intracellular parasite that can survive and multiply within host phagocytes. Brucellosis (undulant fever) is a zoonosis (a disease of animals that may be transmitted to humans). Transmission to humans characteristically occurs either by direct contact with infected animal tissue, or ingestion of unpasteurized milk or milk products, and person-to-person transmission is rare. Clinical significance of Brucellosis (undulant fever): Symptoms are nonspecific and flu-like. If untreated, patients may develop an undulating pattern of fever (temperatures repeatedly rise then fall, hence the name “undulant fever”). Laboratory identification: The organism can be cultured on blood agar. Because the nonspecific symptoms may not point to a diagnosis of brucellosis, a detailed history is often crucial, including the patient’s occupation, exposure to animals, travel to countries where Brucella infection is prevalent, and ingestion of potentially contaminated foods. Treatment: A combination of doxycycline and rifampin is required for prolonged treatment to prevent relapse and reduce the incidence of complications.  5- Legionella Legionella is found in soil and water. Amoebas in water act as reservoirs in which the organism multiplies intracellularly. L. pneumophila is the major cause of disease in man. It causes outbreaks of atypical pneumonia called "Legionnaire's disease" and a mild flu- like condition without pneumonia called Pontiac fever. Legionnaires' disease is severe atypical pneumonia characterized by cough, hypoxia, and fever. The mortality rate is 20 % for healthy individuals and as high as 75% for immune-compromised persons. 6- Bacteroides Pleomorphic group of non-spore forming anaerobic Gram-negative (some weakly or variable staining) bacilli. Bacteroides fragilis is the most important member of the genus which is a major opportunistic pathogen. The infection is characterized by abscess formation. Surgical drainage of pus and removal of necrotic tissue is recommended before treatment.  Bacteria with special cell wall Mycobacteria A- Mycobacterium tuberculosis Characters: - Nonmotile, strictly aerobic, rod or slightly curved, non-spore-forming. - It grows very slowly (generation time 12-24 hrs). -It is cultivated on selective media (Lowenstein - Jensen media). - It is resistant to acid and alkali. It is also resistant to dehydration so it survives in dried sputum. It was only stained by acid-fast (Ziehil Neelsen) stain due to a very long chain of fatty acid (mycolic acid) forming 60% of the cell wall. Do not produce classic endotoxins or exotoxins. The disease results from two host responses (delayed hypersensitivity and cell-mediated immunity). The organism multiplies intracellularly (inside macrophages) thus stimulating cellular immunity. Mode of transmission: - M. tuberculosis is transmitted by droplets and causes pulmonary tuberculosis, while M. bovis is transmitted by ingestion of milk from infected cattle and causes intestinal tuberculosis which is rare. Clinical significance: Mycobacterium tuberculosis infects the lung and is distributed systemically within macrophages. Cord factor damages mitochondria. Tuberculo protein (tuberculin) which combines with other cell wall waxes causes delayed hypersensitivity. a) Pulmonary tuberculosis - The most important pulmonary symptom is cough, which initially may not be productive but becomes productive of sputum as inflammation and tissue necrosis develop. - Chest pain on deep inspiration or coughing. - Granuloma in lung tissue. (caseation of granuloma center). - b) Tuberculosis can occur in the following organs: The intestine, brain, and bones causing osteomyelitis and Lymph nodes.  In first exposure to the bacilli are engulfed by alveolar macrophages, and multiply to form the primary lesion (The Ghon focus). bacilli in macrophages go to the hilar lymph nodes and enlarge. Ghon focus and enlarged hilar lymph nodes form Primary complex. Bacilli are carried by blood, and lymphatics to other organs. Diagnosis: 1) Active disease: Direct smear of clinical sample and staining by Ziehil_Neelsen stain, repeated three times in the morning. Culture on egg-containing medium or selective medium (Lowenstein - Jensen media). PCR or DNA probes hybridization. 2) Latent disease: Tuberculin skin test (Mantoux test): A small quantity of tuberculosis antigens is injected S.C. in the forearm. The test is used within 48- 72 hours. The test is considered positive if the diameter of the resulting lesion is 10 mm or greater. The lesion is characterized by erythema, swelling, and induration (raised and hard). X-rays of the chest. Quantiferon TB GOLD (QFTG): A whole blood test measures the amount of IFN-γ released from macrophages by ELISA test. Treatment The treatment of tuberculosis requires: I. Prolonged course; treatment should be continued for 6-12 months as there is a slow response for treatment. This is due to: a- Most bacilli are intracellular. b- The caseous material interferes with the penetration of the drug. c- In chronic lesions tubercle bacilli are not dividing i.e. "metabolically inactive“ II. Combination of drugs; 2-3 or more drugs are given at the same time: a- To reduce drug toxicity. b- To prevent the emergence of drug-resistant strains. -The first line of treatment drugs are; Isoniazide (INH), rifampicin, ethambutol, and pyrazinamide. -In infections with multiple drug-resistant strains, second-line drugs should be used: streptomycin, para-amino-salicylic acid, ethionamide, and cycloserine. Prevention: vaccination by Bacillus Calmette–Guérin (BCG) (living attenuated M. bovis strain).  B- Mycobacterium leprae Characters: - - Nonmotile, aerobic rod-shaped surrounded by the characteristic waxy coating unique to Mycobacteria. - The organism infects the skin, because of its growth at low temperature. - M. leprae has never been grown in artificial culture but will grow in the footpads of mice and in armadillos (which have a low body temperature). M. leprae is the causative agent of leprosy (Hansen's disease). - Infection is acquired by prolonged contact with patients with lepromatous leprosy who discharge M. leprae in large numbers in nasal secretions and from skin lesions. armadillos Clinical significance: There are two distinct forms of infections: ❖ Tuberculoid leprosy: Mild form. Characterized by damaged nerves and areas of skin without sensation, destruction of hair follicles and sweat glands. This most affects the fingers and toes resulting in falling off. ❖ Lepromatous leprosy: Very progressive. Large numbers of bacteria in skin cells result in cell death and a loss of facial features resulting in leonine faces. Freely multiply in the skin causing nodules to form all over the body. Nerves are less damaged than in the Tuberculoid form. Diagnosis: The bacilli are easily demonstrated by performing acid-fast stain of skin lesions or nasal scrapings. Treatment and prevention: Dapsone (diamino diphenyl sulfone) has been successfully used for over fifty years to treat leprosy, but recently, the bacilli have become more resistant to the treatment. Multidrug therapy usually consisting of rifampicin, clofazimine, and dapsone, is used. Leprosy can be avoided by covering the face and hands in the presence of infected individuals with isolation of patients. Vaccination with BCG has shown a protective effect.  Atypical Bacteria Because they are so small and can grow only within living cells, they were originally thought to be viruses. However, they share characteristics with bacteria including possessing both RNA and DNA, multiplying by binary fission, possessing ribosomes, contains various enzymes concerned with metabolism, and their growth can be inhibited by antimicrobial drugs. A- Mycoplasma and Ureaplasma Characters: - Mycoplasma and Ureaplasma are two human pathogens under the family Mycoplasmataceae - Mycoplasmas are the smallest free-living bacteria. They range from 0.2 - 0.8 µm and thus can pass through some filters used to remove bacteria. - They require complex media for their isolation. A characteristic feature that distinguishes the mycoplasmas from other bacteria is the lack of a cell wall. Thus, they can assume multiple shapes including round, pear- shaped, and even filamentous. - Mycoplasmas are facultative anaerobes, except for M. pneumoniae, which is a strict aerobe. Moreover, Ureaplasma aromaticum is aerobic. Organism Disease M. pneumoniae Upper respiratory tract disease, tracheobronchitis, atypical pneumonia. M. hominis Pyelonephritis, pelvic inflammatory disease, postpartum fever M. genitalium Nongonococcal urethritis. U. urealyticum Nongonococcal urethritis.  B- Rickettsia 1- Gram-negative short bacilli but stain very poorly and are best demonstrated by Giemsa (blue) or Macchiavello stain (red). They are aerobic. 2- They do not grow on culture media but grow readily in embryonated eggs (with a generation time of 8-10 hrs. at 32°C) and in tissue cells. 3- All rickettsial diseases are zoonoses (have an animal reservoir as it is acquired through the bite of an infected arthropod). 4- They are obligate intracellular bacteria, that can cause diseases: Typhus (R. prowazekii) Rocky mountain spotted fever (R. rickettsia). Diagnosis: PCR  C- Coxiella 1- They are highly resistant to heat, UV, and drying, probably due to the formation of endospore-like structures. They are aerobic, and Gram-negative. 2- Transmission is mainly by inhalation of airborne infectious dust or drinking contaminated unpasteurized milk. 3- Example of disease: Q fever caused by Coxiella burnetii (primarily affects lungs). Chronic Q fever infection requires months of antibiotic treatment. Chronic Q fever is more likely to occur in people with heart valve disease, blood vessel abnormalities, or in people with weakened immune systems. Women infected during pregnancy may also be at risk for developing chronic Q fever.  D- Chlamydia 1- They have a rigid cell wall with high lipid content, but it does not contain peptidoglycan. 2- They are aerobic, Gram-negative, and obligate intracellular bacteria. 3- They stain very poorly with gram stain and are best demonstrated by Giemsa (blue) or Macchiavello stain (red). 4- They are usually cultivated in the yolk sac of embryonated eggs, but some will grow in cell cultures and various animal tissues. 5- pathogenic species: Chlamydia psittaci (respiratory tract infection), Chlamydia trachomatis (Infection of the eye and genitals. Chlamydia pneumonia (respiratory tract infection). Note: Most atypical bacteria are treated by Doxycycline, chloramphenicol, or macrolides according to the sensitivity patterns. Bacteria with flexible cell wall 1. Spirochetes The spirochetes are all long, slender, helically curved, Gram-negative bacilli, with the unusual morphologic features of axial fibrils and an outer sheath. - Unlike typical Gram-negative bacteria, most spirochetes, including T. pallidum, do not have lipopolysaccharide (LPS), or endotoxin, in the outer leaflet of the outer membrane. Aerobic or microaerophilic or anaerobic. - These fibrils, or axial filaments, are flagella-like organelles that facilitate the motility of the organisms (corkscrew-like manner) Spirochetes that are important human pathogens are confined to three: 1. Treponema (Treponema pallidum causes syphilis). 2. Borrelia (Borrelia burgdorferi causes Lyme disease. Borrelia recurrentis and Borrelia hermsii causes relapsing fever). 3. Leptospira (Leptospira interrogans cause leptospirosis). A-Treponema pallidum The causative organism of syphilis is extremely fastidious and fragile. It cannot be cultured in cell-free systems and is sensitive to disinfectants, heat, and drying. The organism is only weakly antigenic. T. pallidum secretes hyaluronidase, an enzyme that disrupts ground substances and probably facilitates the dissemination of the organism. Transmission: by sexual contact or transplacental (congenital syphilis). Clinical significance: Causes syphilis, a chronic and slowly progressive disease. The disease is divided into stages: 1- Primary syphilis (chancre): 10-60 days after infection, a painless ulcer appears usually at the site of inoculation, most commonly the genitalia. Within 3 to 6 weeks, the chancre heals. Then, dissemination of the organism occurs. 2- Secondary syphilis: Starts 2 to 10 weeks after the chancre appears. Symptoms include skin rash, enlargement of lymph nodes, and generalized mucus membrane patches. Other symptoms may include fever, sore throat, malaise, weight loss, hair loss, and headache. 3- Latent syphilis: Latent syphilis is defined as having serologic proof of infection without symptoms of the disease. Latency sometimes continues for life or tertiary syphilis may occur. 4- Tertiary syphilis (Several years): Occurs within 3 to 15 years after the initial infection in up to 35% of untreated patients and may be divided into three different forms: Gummatous syphilis (15%), chronic gummas, which are soft, tumor-like balls of inflammation that vary in size. Late neuro-syphilis in the form of syphilitic meningitis. Cardiovascular syphilis. Diagnosis: -Microscopy (dark-field examination or direct fluorescent antibody staining). - Serodiagnosis that measures the presence of two types of antibodies: a) Treponemal antibodies. - Enzyme immunoassay (EIA). - FTA-ABS test Fluorescent (Treponemal antibody absorption test) b) Nontreponemal antibodies. (Reaginic antibodies) are produced by infected patients against components of mammalian cells (cardiolipin-lecithin). These tests are used for screening purposes. The most widely used nontreponemal serologic test is the VDRL (Venereal Disease Research Laboratory) test: cardiolipin forms visible clumps when combined with reagain antibodies. Treatment: For all treponemal infections, penicillin G is the drug of choice. Tetracycline, or erythromycin in patients allergic to penicillin.  B- Borrelia - Like T. pallidum, Borrelia does not produce endotoxin or exotoxins. Diseases: I- Relapsing Fever: There are two major forms of relapsing fever: Tick-borne relapsing fever (B. duttoni, B. hermsii and B. parkeri) and Louse-borne relapsing fever (B. recurrentis). Pathogenesis: A few days after infection, patients have an abrupt onset of fever, headache, and myalgia. As the host produces a specific antibody in response to the agent, organisms disappear from the bloodstream, becoming sequestered (hidden) in different body organs during the afebrile period. Subsequently, organisms reemerge with newly modified antigens and multiply, resulting in another febrile period.  Subsequent relapses are usually milder and of shorter duration. Diagnosis: based on the appearance of Giemsa or Wright stainable, loosely coiled spirochetes in the blood during the febrile stage of the disease. Treatment: Tetracyclines, erythromycin, and penicillin. II- Lyme disease 1. The first stage: erythema migrans (EM), is the characteristic red, ring-shaped skin lesion with a central clearing that first appears at the site of the tick bite but may develop at distant sites as well. Patients may experience headaches, fever, muscle and joint pain, and malaise during this stage. 2. The second stage (weeks to months after infection) may include arthritis and neurologic disorders (meningitis and carditis). 3. The third stage: Is characterized by chronic arthritis and may continue for years. Laboratory identification: B. burgdorferi can be cultured, but the procedure is difficult and takes 6 to 8 weeks. Two-step test serologic diagnosis: The first step: is a sensitive screening test (ELISA or Indirect Fluorescent Antibody IFA) ❑ If this test is positive or equivocal, the result must be confirmed by immunoblotting (second stage). Treatment: Stages I and II: amoxicillin, cefuroxime, doxycycline, or a macrolide. Stage III: ceftriaxone.  C- Leptospira Leptospira interrogans is the main pathogenic species. Leptospirosis, a zoonosis, humans become infected through direct or indirect contact with the urine or blood of infected animals. The most common clinical syndrome is: 1- Anicteric leptospirosis: a self-limiting illness consisting of a septicemic stage, with high fever and severe headache that lasts 3 to 7 days, followed by the immune stage. 2- WEIL’S DISEASE (Infectious Joundice): caused by L. icterohemrrhagia. Symptoms are caused by liver, kidney, and/or vascular dysfunction and lethal pulmonary hemorrhage. Diagnosis: Serologic agglutination tests Visual demonstration of the spirochetes in urine, blood, or cerebrospinal fluid. Treatment: Penicillin or doxycycline.