PHARMACEUTICAL MICROBIOLOGY -1I PHT 313 Dr. Rasheeda HamidAbdalla Assistant Professor E-mail rasheedahamed12@hotmail.com

Rickettsiae

Objectives Rickettsiae Chlamydiae Mycoplasma

Rickettsiae The group of organisms known as rickettsiae (family Rickettsiaceae) consists of three genera: Rickettsia Ehrlichia Coxiella

Rickettsiaceae Rickettsia, Ehrlichia, and Coxiella have a number of features in common: They grow only inside living host cells (obligately intracellular parasites) Most rickettsial infections are tansmitted by infected arthropods Rickettsial diseases are generalized infections

General characteristics They are small, rod like or coccobacillary shaped Have a typical double-layered gram-negative cell wall. Visualized under the light microscope with one of the polychrome stains, such as Giemsa

Pathogenesis Parasitized endothelial cells through out the circulatory system Transmitted to human by arthropods (fleas, ticks, mites, or lice). Reservoirs are rodents, humans, or arthropods Following a bite the organisms are taken into cells by a process similar to phagocytosis. The organism produce phospholipase that damage host cell membrane ,and facilitate cell entry

Pathogenesis (cont’d) The organisms multiply in both the nucleus and cytoplasm of host cells. host cells are killed, and rickettsia spread throughout the body Focal thrombi are formed in various organs including the skin Variety of small hemorrhages and hemodynamic disturbances created the symptoms of the illness

Clinical significance 1-Rocky Mountain spotted fever Caused by Rickettsia rickettsii Human infection is initiated by the bite of an infected wood or dog tick

Clinical significance Symptoms: High fever Malaise Prominent rash In untreated cases, vascular disturbances and myocardial or renal failure may ensue.

Rocky mountain spotted fever rash

Clinical significance (cont’d) 2-Other spotted fevers: Tick-borne spotted fevers similar to Rocky Mountain spotted fever They vary in severity Caused by R. conorii, R. canada, and R. sibirica 3-Louseborne (epidemic) typhus is caused by Rickettsia prowazekii [Note: Epidemic typhus is a different disease from salmonella-induced typhoid fever

Clinical significance (cont’d) 4-Other forms of typhus-like fever: Murine (endemic) typhus Caused by R. typhi, is a clinically similar, but usually milder disease than that caused by R. prowazekii

Laboratory identification Serological tests Infected cells detection by immunofluorescence or histochemical procedures on some clinical samples, such as punch biopsies from areas of rash

Treatment Doxycycline is the drug of choice for the treatment of Rocky Mountain spotted fever in both adults and children, except for pregnant women who should be treated with chloramphenicol

Prevention of infection Prevention depends on vector control Personal protection Vaccines are not currently licensed for use in the United States

Coxiella Coxiella burnetii,the causal agent of Q fever Transmission to human: Inhalation of infected dust Via other mucous membranes, abrasions Gastrointestinal tract through consumption of milk from infected animals.

Clinical significance C. burnetii reproduces in the respiratory tract and then (in the absence of treatment) is disseminated to other organs. Classic Q fever is an interstitial pneumonitis

Laboratory identification Serologic assays are the principal means of specific diagnosis. Treatment and prevention Doxycycline is the drug of choice for treatment. A vaccine has been reported to be of limited use in occupationally exposed individuals.

Chlamydiae Chlamydia is a genus of small bacteria Obligate intracellular parasites They grow in cytoplasmic vacuoles The genus is divided into three species: Chlamydia trachomatis, Chlamydia psittaci, Chlamydia pneumoniae. ..

C. trachomatis cause diseases of Genitourinary tract, including many cases of nongonococcal urethritis Ocular infections such as trachoma. C. psittaci and C. pneumoniae infect the respiratory tract. C. psittaci causes psittacosis (parrot fever,) C. pneumoniae causes atypical pneumonia

General Features of Chlamydiae Chlamydiae are small Round-to-ovoid Chlamydial cell wall resembles a gram-negative envelope possess ribosomes and synthesize their own proteins and, therefore, are sensitive to antibiotics that inhibit this process, such as tetracyclines and macrolides

Pathogenesis The extracellular infectious form, the elementary body The elementary body is taken up by phagocytosis into host cells, The elementary body prevents fusion of the phagosome and lysosome The particle reorganizes into a larger, noninfectious reticulate body Reticulate body divides, forming an inclusion body. Reticulate bodies condense to become new infectious elementary bodies. The elementary bodies released from the cell by cytolysis, ending in host cell death

Laboratory identification Direct immunofluorescence is also a common and useful procedure In C. trachomatis only, a matrix of glycogen like material accumulates in the inclusions, which can be shown by staining with iodine.

Clinical significance Chlamydia trachomatis: divided into a number of serotypes, which correlate with the clinical syndrome they cause C. trachomatis causes: Genitourinary infections Eye infections

Genitourinary infections 1-Nongonococcal urethritis (NGU) Transmission: Sexual contact During birth In males, the urethra is the principal locus of infection Females may present with cervicitis and/or urethritis

Genitourinary infections (cont’d) 2-Lymphogranuloma venereum (LGV): Invasive sexually transmitted disease causes by C. trachomatis serotypes L1, L2, and L3

Eye Infection 3-Trachoma inflamed granulation on the inner surface of the lids. 4-Neonatal conjunctivitis and other infections 5-Inclusion conjunctivitis in adults

Laboratory identification -Direct tests: Microscopic examination using direct fluorescent antibody staining reveals characteristic cellular cytoplasmic inclusions -Culturing in tissue culture -PCR -Detection of serotypes: by immunofluorescence staining with monoclonal antibodies

Treatment and prevention Azithromycin and tetracycline are currently the drugs of choice Erythromycin used in small children and pregnant women because of the effects of tetracyclines on calcification A topical ocular preparation containing erythromycin effective prophylaxis in newborns Detection a particular problem in asymptomatic individual followed by specific treatment is the key means of control.

Chlamydia psittaci Psittacosis (ornithosis) a zoonotic disease Transmitted to humans by inhalation of dust contaminated with respiratory secretions or feces of infected birds. Affect lower respiratory tract Causing fever, dry cough, and flulike symptoms bilateral patchy pulmonary infiltration Enlargement of liver and spleen is a frequent accompanying feature Doxycycline or erythromycin is effective in eradicating symptoms

Chlamydia pneumoniae Chlamydia Pneumoniae C. pneumoniae is a respiratory pathogen causing pharyngitis, sometimes followed by laryngitis, bronchitis, or interstitial pneumonia. The organism is sensitive to doxycycline and erythromycin

Mycoplasma Mycoplasma species : Distributed in nature Commensals found in the mouth and genitourinary tract of humans and other mammals Three Mycoplasma species associated with human disease

Mycoplasma pneumoniae which is the cause of a primary atypical pneumonia, Mycoplasma hominis Ureaplasma urealyticum which are associated with a variety of genitourinary diseases, such as Urethritis pelvic inflammatory disease, and intrapartum infections

General Features of Mycoplasmas Lacking cell walls, Mycoplasmas are enclosed instead by a membrane composed of a lipid bilayer pleomorphic. can be grown in cell-free media medically important species are facultative anaerobes some genus members are strict anaerobes Fastidious Require cholesterol and fatty acids for growth

Mycoplasma Pneumoniae M. pneumoniae is transmitted by respiratory droplets causes a lower respiratory tract infection (unlike typical lobar pneumonia) bronchitis, pharyngitis, nonpurulent otitis media

Pathogenesis M. pneumoniae possesses a membrane-associated protein, P1, which functions as a cytoadhesin. which binds to ciliated bronchial epithelial cells. and inhibit ciliary action. affected mucosa desquamate, and an inflammatory response develops in bronchial and adjacent tissues The disease is an expression of host-specific immune response rather than damage created by the organism itself. In infected individuals, organisms are shed in saliva for several days before onset of clinical illness.

Clinical significance Primary atypical pneumonia (lower respiratory tract disease) is the best known form of M. pneumoniae infection (walking pneumonia) Upper respiratory tract and ear infection more frequent

cont’d)) Clinical significance Symptoms : headache, fever, chills, and malaise. dry or scantily productive cough. Earache In the absence of preexisting compromise the disease remits after 3-10 days without treatment Complications are rare, but include CNS disturbances, a rash and mild, hemolytic anemia

Laboratory identification Sputum samples or throat swabs can be cultured on special media Serologic test.

Treatment M. pneumoniae is sensitive to doxycycline or azithromycin.

Genital Mycoplasmas Mycoplasma hominis Ureaplasma urealyticum Are common inhabitants of the genitourinary tract The major clinical condition associated with M. hominis is postpartum or postabortal fever U. urealyticum causes urethritis in men. In women causes endometritis. M. hominis resistant to erythromycin, in contrast to other mycoplasmas. Tetracycline is effective for specific treatment.

Other Mycoplasmas AIDS-associated mycoplasma, or M. incognitus

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