Mycoplasma

ubiquitous as pathogens and colonizing agents in the plant, animal, and insect kingdoms smallest known free-living forms difficult to culture on a cell-free medium

General
Prokaryotic Small size: 150-250 nm No cell wall Trilayered cell membrane Most are aerobic Fastidious growth requirements Form fried egg colonies on agar

UNCOMMON MYCOPLASMA ASSOCIATED WITH HUMAN DISEASE

 Mycoplasma incognitus (a variant of M. fermentans) Mycoplasma penetrans Mycoplasma pirum Mycoplasma fermentans severe disease in healthy people and those with acquired immunodeficiency syndrome (AIDS)

Mycoplasma pneumoniae and Atypical Pneumonia

 onset of the antibiotic era In the early 1940s, sulfonamides and then penicillins were introduced into clinical practice pneumonia did not respond to these antibiotics pneumonias that could not be attributed by Gram stain or culture primary atypical pneumonia (PAP).

Epidemiology
singly or as family outbreaks with a high rate of secondary infection closed populations such as military recruit camps and boarding schools mycoplasma can cause miniepidemics and may represent from 25% to 75% of pneumonias in such settings

 United States, mycoplasma pneumonia occurs for each

1000 persons, or more than 2

million

cases annually. mycoplasma nonpneumonic respiratory infection may be 10 to 20 times

 highest attack rates are in individuals 5 to 20 years old, but M. pneumoniae infection can occur at any age and may cause particularly severe disease in neonates

 age-related incidence of upper versus lower respiratory tract infection caused by M.pneumoniae. Children younger than 3 years of age develop primarily upper respiratory tract infection

5 to 20 years old tend to develop bronchitis

and pneumonia. In older infected adults pneumonia is relatively common.

Transmission
M. pneumoniae infection is spread from one patient to another by respiratory droplets produced by coughing. incubation period of 2 to 3 weeks.

RESPIRATORY INFECTION
M. pneumoniae infections lead to clinically apparent disease rather than to subclinical infection, and most involve only the upper respiratory tract. After a - to week incubation period, insidious onset manifested by fever, malaise, headache, and cough. cough is a clinical hallmark of M. pneumoniae infection. The frequency and severity of cough increase over the next 1 to 2 days and may become debilitating. The gradual onset of symptoms is in contradistinction to the often acute presentation of respiratory infection caused by influenza, adenovirus, and other respiratory viruses.

 5% to 10% of patients,

the infection progresses to tracheobronchitis or pneumonia. In these cases, the original manifestations persist, and the cough becomes more severe. nonproductive, white or occasionally bloodflecked sputum. Gram staining of this sputum reveals evidence of inflammatory cells but no predominant bacterial species.

 parasternal chest soreness due to muscle strain true pleuritic pain is unusual Fever is usually at 101 to 102 F and may be associated with chilly sensations myalgias and gastrointestinal complaints of nausea and vomiting are unusual.

physical examination
walking pneumonia pharynx may be injected and erythematous without the marked cervical adenopathy seen in group A streptococcal pharyngitis. bullous myringitis No auscultative or percussive findings on chest exam or minimal rales Pleural effusion (usually small) occurs in 5% to

20%

mild and self-limited

EXTRAPULMONARY INVOLVEMENT
DERMATOLOGIC INVOLVEMENT macular morbilliform papulovesicular eruptions erythema nodosum urticaria

 erythema multiforme major, or StevensJohnson syndrome (up to 7%)

Erythema multiforme major consists of erythematous vesicles, plaques, and bullae involving the skin, with particular localization at mucocutaneous junctions.

Stevens-Johnson syndrome

Raynaud phenomenon

Necrosis of distalextremities in a patient with sickle cell disease

CARDIAC COMPLICATIONS
most common extrapulmonary manifestations arrhythmia, congestive failure, chest pain, and electrocardiographic abnormalities conduction defects mechanism of heart damage is unknown, but M. pneumoniae has been isolated from the pericardial fluid of one patient.

NEUROLOGIC COMPLICATIONS
Encephalitis aseptic meningitis meningoencephalitis transverse myelitis brain stem dysfunction Guillain-Barr syndrome peripheral neuropathy

 The cerebrospinal fluid findings in these cases are variable, but cellular response is usually minimal, with slightly elevated protein and normal to slightly depressed glucose. diagnosis of mycoplasma-related central nervous system involvement is made on exclusion of other causes, presence of antecedent or intercurrent respiratory illness, and a rise in antibody titer to M. pneumoniae in the serum. Occasionally, mycoplasma-specific antibodies have been demonstrated in the cerebrospinal fluid, but these titers have paralleled serum antibody titers.

MUSCULOSKELETAL, RENAL, AND HEMATOPOIETIC COMPLICATIONS

Polyarthralgias arthritis is rare:monoarticular or migratory Renal complications associated with immune complex deposition and high-titer cold agglutinin There are several case reports of M. pneumoniaeassociated aplastic anemia

CONDITIONS LEADING TO INCREASED SUSCEPTIBILITY

sickle cell disease or sickle-related hemoglobinopathies These patients may develop large pleural effusions and marked respiratory distress. Functional asplenia

Immunology
stimulating several components of the immune system mycoplasma-induced cold agglutinins develop early in the disease (7 to 10 days) The titer of these agglutinins peaks at 2 to 3 weeks and persists for 2 to 3 months

Diagnosis
Culture requires 1 to 2 weeks for definitive results IgM antibodies positive 1 to 2 weeks after the infection real-time PCR, performed on sputum, nasopharyngeal aspirate or throat swab material The cold agglutinin assay

cold agglutinin assay

A titer of 1 : 32 or greater is highly suggestive of infection with M.pneumoniae mononucleosis caused by Epstein-Barr virus (anti-i), cytomegalovirus (anti-I) some other viral diseases, and lymphoma

 A rapid bedside version of this test can be performed easily by any health care provider. In this test,1 mL of the patient's blood is drawn into a tube containing anticoagulant. Before cooling, examination shows a smooth coating of the tube by red cells. The blood is cooled to 4 C by placing it on liquid ice or in a standard refrigerator. After 3 to 4 minutes, the tube is examined for the presence of macroscopic agglutination. The tube is then rewarmed to 37 C in an incubator, or by exposure to body heat, and reexamined. The agglutination should dissociate at 37 C. This temperature-associated agglutination and dissociation can be repeated many times on the same sample A positive result in the bedside test correlates with a laboratory titer of 1 : 64

Treatment
antimicrobial therapy remains empirical as part of CAP therapy Antimicrobial therapy is not necessary for mycoplasmal upper respiratory tract infection treatment with effective antimicrobials can markedly shorten the illness and, by reducing cough and the number of organisms reduce the spread of infections in contacts

macrolides and tetracyclines :Doxycycline fluoroquinolones macrolide-lincomycin-streptograminketolide (MLSK)

macrolide-resistant M. pneumoniae (mutation in 23 s rRNA,variation in the P1adhesin gene,)

Recommended standard
teenagers and adults would include - doxycycline,

100 mg every 12 hours

- extended-spectrum macrolide such as azithromycin, 500 mg on day 1, and then 250 mg every 24 hours. The usual duration of therapy is 7 to 14 days. Young children - erythromycin, 10 mg/kg every 6 hours - extended spectrum macrolide (azithromycin), 10to12 mg/kg on day 1, followed by 5 mg/kg daily for 10 to 14 days.

Genital Mycoplasmas

Prevalence of Genital Mycoplasmas in Healthy People

Ureaplasmas are highly prevalent in the genital tracts of healthy sexually active women U. parvum strains account for 70% of ureaplasmas detected in the male urethra is lower at 10% to 20%. Infants can be infected with ureaplasmas at birth. The organisms persist for a while and disappear by age 2 years. Ureaplasmas become prevalent with the onset of sexual activity in both males and females.

Mycoplasmas and Nongonococcal Urethritis in Men

recognized that urethritis persisted in some cases after treatment with penicillin and elimination of gonococci. U. urealyticum or U. parvum are major cause chlamydiae are associated with 30% M.genitalium with 20%

Mycoplasmal Infections in Women

ureaplasmas in the vagina of healthy sexually active women (66%) commensals and normal flora M. genitalium is associated with a proportion of the same diseases that C. trachomatis is associated with

CULTIVATION AND DETECTION

PCR culture is slow and difficult

 M. hominis detected in the vagina or male urethra can best be interpreted as normal flora. M.genitalium implies potential disease

Chlamydia and Chlamydophila

nomotile, obligate intracellular prokaryotic organisms with a unique biphasic life cycle

Chlamydia trachomatis
Trachoma Perinatal Infection Lymphogranuloma Venereum, and Other Genital Infections

Reported incidence of Chlamydia trachomatis in the United States.

 (1) Electron-dense elementary bodies (EBs) attach to

and are taken bodies (RBs). up by epithelial cells.

(2) Inclusions fuse and EBs differentiate into reticulate (3) RBs divide by binary fission. (4) RBs re-form into EBs. (5) EBs released, often with cell death, to infect other
cells.

(6) Alternate course under stressful conditions (i.e., IFN exposure) leading to large, metabolically inactive persistent forms. infectious state.

(7) With removal of stress, return to replication and

Laboratory Diagnosis
classic trachoma can be diagnosed on clinical grounds alone cytologic examination for intracytoplasmic inclusions isolation of C. trachomatis in cell culture demonstration of chlamydial antigen by enzyme-linked immunosorbent assay or by immunofluorescent staining demonstration of nucleic acid by direct hybridization or by amplification techniques

cytologic examination for intracytoplasmic inclusions

infant inclusion conjunctivitis and in ocular trachoma, typical intracytoplasmic inclusions can often be identified in Giemsa-stained cell scrapings from the conjunctiva.

ISOLATION IN CELL CULTURE

C. trachomatis grows well in a variety of cell lines(McCoy or HeLa cells) Incubation in cell culture ranges from 40 to 72 hours

Clinical Manifestations
classic ocular trachoma LGV oculogenital diseases in adults perinatal infections

OCULAR TRACHOMA
first infection usually occurs early in life (generally before age 2 years), and active disease persists for several years initial infections may resolve spontaneously complicated by reinfection or by superimposed bacterial conjunctivitis

 In its initial stages, trachoma manifests as a chronic follicular conjunctivitis with papillary hypertrophy and inflammatory infiltration. the disease progresses, scarring of the conjunctiva occurs, and there is involvement of the cornea. the inner surface of the lids becomes scarred the eyelashes turn in and abrade the cornea, resulting in ulceration, scarring, and visual loss. Children with mild disease are left with some conjunctival scarring and pannus formation (fibrovascular infiltrate), whereas others develop badly scarred conjunctivae and corneas. The latter may not occur until well into adult life

Treatment
In endemic areas, the primary reservoir is children with ocular infection.[187] Transmission occurs by hand-to-eye contact S-A-F-E strategy -surgery for deformed eyelids -periodic mass treatment of villages with the antibiotic azithromycin - face washing and hygiene -environmental improvements to control flies by such techniques as building latrines outside villages

LYMPHOGRANULOMA VENEREUM
LGV is a sexually transmitted disease caused by the LGV serovars of C. trachomatis stages in classic LGV The first stage is formation of a primary lesion, usually on the genital mucosa or adjacent skin. a small papule or herpetiform ulcer that produces few or no symptoms appears between 3 and 30 days after acquisition of infection heals rapidly without leaving a scar. Initial infection can also be intraurethral, producing a symptomatic urethritis; cervical, producing cervicitis; or rectal, causing proctitis.

secondary stage
occurs days to weeks after the primary lesion lymphadenopathy and systemic symptoms. The lymph nodes involved are those that drain the area of the primary lesion and thus depend on its location. In men, the primary lesion is usually on the penis or in the urethra, and thus the inguinal lymph nodes are the main ones affected. unilateral in two thirds

 lymph nodes are discrete and tender with overlying erythema forming an inflammatory mass. Abscesses within the mass coalesce forming a bubo that may rupture spontaneously with development of loculated abscesses, fistulas, or sinus tracts Systemic manifestations are often associated with this phase, including fever, headache, and myalgias. meningitis organism has been recovered from blood or cerebrospinal fluid

third stage
Esthiomene: hypertrophic chronic granulomatous enlargement with ulceration of the external genitalia (either the vulva or scrotum and penis) Lymphatic obstruction may also lead to elephantiasis of the male or female genitalia.

Treatment of Lymphogranuloma Venereum 21 days of doxycycline, 100 mg twice

daily, with erythromycin or sulfisoxazole listed as alternative regimens In addition, fluctuant buboes should be aspirated to prevent rupture and sinus tract formation Effects on late complications such as strictures are variable.

Chlamydophila (Chlamydia) psittaci (Psittacosis)

Psittacosis is a systemic infection that frequently causes pneumonia relationship to bird exposure

Clinical Findings and Differential Diagnostic Considerations

incubation period of 5 to 15 days manifestations tend to be nonspecific atypical pneumonia, with nonproductive cough, fever, headache, and chest film abnormalities Fever, CoughHeadache, myalgias, and chillsconfusing: diaphoresis, photophobia, tinnitus, ataxia, deafness, anorexia, nausea and vomiting, abdominal pain, diarrhea, constipation, sore throat, dyspnea, hemoptysis, epistaxis, arthralgia, and rash. Chest soreness is reported, but true pleuritic pain is rare

Specific end-organ involvement reflects the systemic nature of psittacosis

most commonly involved in humans is the lung. Cardiac manifestations include pericarditis (rarely with effusion and tamponade), myocarditis, idiopathic dilated cardiomyopathy, and culture-negative endocarditis Hepatitis, jaundice, hemolysis, DIC, Reactive arthritis Neurologic abnormalities

 Dermatologic phenomena include Horder's spots, which are a pink, blanching, maculopapular eruption

Diagnosis
CDC consider a confirmed case one with a compatible clinical illness plus laboratory confirmation by one of the following a titer of 1 : 16 with microimmunofluorescence (MIF) IgM, culture from respiratory secretions fourfold or greater rise in complement-fixing (CF) or MIF antibody to a titer of 1 : 32 in specimens drawn 2 weeks apart. A probable case is one associated with a compatible illness linked epidemiologically to a confirmed human case or a titer of at least 1 : 32 in a single specimen by CF or MIF.

Treatment
tetracycline hydrochloride four times daily

500 mg PO

doxycycline 100 mg PO twice daily

10 to 21 days

Chlamydophila (Chlamydia) pneumoniae

Clinical Manifestations
mild or asymptomatic or atypical pneumonia associated with severe illness and even death, although the role of preexisting chronic conditions The relationship of C. pneumoniae and upper respiratory infections, including pharyngitis, sinusitis, and otitis media, is less clear.

 in adults, doxycycline, 100 mg orally twice daily for 14 to 21 days tetracycline, 250 mg orally four times daily for 14 to 21 days azithromycin, 1.5 g orally over 5 days clarithromycin, 500 mg orally twice a day for 10 days levofloxacin, 500 mg, intravenously or orally once a day for 7 to 14 days moxifloxacin, 400 mg orally once a day for 10 days. For children, erythromycin 10 to 14 days; clarithromycinsuspension 10 days; or azithromycin suspension 5 day

C. PNEUMONIAE AND CHRONIC DISEASE IN HUMANS

asthma arthritis atherosclerosis