Actinomycosis

It is a subacute-to-chronic infectious disease characterized by multiple draining sinuses that is mainly caused by Actinomyces israelii. It is characterized by contiguous spread, suppurative and granulomatous inflammatory reaction, and formation of multiple abscesses and sinus tracts with discharging sulfur granules.

Etiology: Actinomyces are anaerobic gram positive rod shaped or filamentous branching bacteria that are not acid fast. They are often present as comensals in the oral cavity on the gums, tonsillar crypts, and teeth (dental plaque) and less so in the lower gastrointestinal tract and female genital tract. Important species of Actinomyces are A. israelii, A. bovis, A. viscosus, A. naeslundii and A. meyeri. Other actinomycetes include Arachnia propionica and Bifidobacterium dentium.
Most infections are polymicrobial, with other bacteria (oral anaerobes, staphylococci, streptococci, or Enterobacteriaceae) frequently cultured from lesions.

Pathogenesis: Since these microorganisms are not virulent, they require a break in the integrity of the mucous membranes and the presence of devitalized tissue to invade deeper body structures and cause human illness. Establishment of human infection may require the presence of other bacteria, which participate in the production of infection by producing a toxin or enzyme or by inhibiting host defenses. These companion bacteria appear to act as co-pathogens, which enhance the relatively low invasive power of actinomycetes. Once infection is established, the host mounts a suppurative, granulomatous response, and fibrosis develops subsequently. Infection typically spreads contiguously, invading surrounding tissues or organs. Ultimately, the infection produces draining sinus tracts. Hematogenous dissemination to distant organs may occur in any stage of the infection. Actinomycosis most often occurs in adult males.

Types of actinomycosis:

• Cervicofacial actinomycosis

• Thoracic actinomycosis

• Abdominal actinomycosis

• Pelvic or uterine actinomycosis

• Dental and periodontal diseases

Cervicofacial actinomycosis:
Cervicofacial (lumpy jaw) form is the most common form. Infection typically occurs following oral surgery or in patients with poor dental hygiene. Organism enters through trauma to mucus membrane of the mouth or pharynx by way of carious teeth or through tonsils. Initial symptoms are pain and swelling along alveolar ridges and of the soft-tissue in perimandibular area. Direct spread into the adjacent tissues occurs gradually. Regional lymph nodes swell, become firm, nodular ("wooden" or "lumpy"). Subsequently, areas of softening appear and develop into sinuses and fistulas with a discharge that contains the characteristic sulfur granules.
Bone involvement is a characteristic feature resulting in periostitis followed by oseteomyelitis. Infection in maxilla may extend to cranial bones giving rise to meningitis or into orbit and middle ear. Mandibular disease invades tongue and sublingual salivary glands. Direct extension into lung and pleural cavity may occur. 

Thoracic actinomycosis:
Aspiration of oropharyngeal secretions containing actinomycetes is the usual mechanism of infection. Thoracic actinomycosis may result from extension from neck, thorax, abdomen or via hematogenous spread from a distant lesion. Thoracic actinomycosis may resemble tuberculosis. Commonly affected region in the lungs are hilar region and basal parenchyma. Initial symptoms are that of subacute pulmonary infection with mild fever, cough with purulent sputum but without hemoptysis. As the disease progresses, small abscess develop in the lung and sputum becomes blood-streaked. Infection spreads to pleura and thoracic wall and then penetrates the surface to form typical discharging sinuses. Pleural effusion may occur. Ribs may undergo destructive changes. Hematogenous spread may result in peripheral cutaneous and subcutaneous abscesses. 

Abdominal actinomycosis: 
In the abdominal form, the intestines (usually the cecum and appendix) and the peritoneum are infected. This may result from perforation of intestinal wall by fish and chicken bones, knife, gunshot injury or surgery. Most frequent source is the diseased appendix. The ileocecal region is involved most frequently, and the disease presents classically as a slowly growing tumor. Initial symptoms are insidious and related to involved organ. Pain, fever, vomiting, diarrhea or constipation, and emaciation are characteristically present. Extension to liver may result in jaundice. Extension may occur to kidney, gall bladder or backbone. Extension to the anterior abdominal wall with formation of multiple draining sinus tracts may occur.

Pelvic or uterine actinomycosis: 
This is a disease of uterus, cervix and vagina that is associated with use of IUD. In most cases, an IUCD has been in place for an average of 8 years. Masses may occur on ovary or fallopian tube. Symptoms include abdominal masse, vaginal discharge along with pelvic or lower abdominal pain.

Dental and periodontal disease:
Plaque is deposited by Streptococcus sps in which various other bacteria are included. Plaque formation, both supragingival and subgingival is initial step in caries development. 

Other:
Direct inoculation into the skin may result in actinomycotic mycetoma. Primary infection of skin results from human bites, barbed wire, fist fights, hypodermic needles etc. dissemination from primary focus to bladder, kidney, humerus, heart valve and CNS may occur.

Laboratory diagnosis:
Specimen collection: Specimen collected depends on the site of infection. Specimen material is obtained from draining sinuses, deep needle aspirate or biopsy specimens. Swabs, sputum, and urine specimens are unacceptable or inappropriate. 

Direct examination: Direct examination for sulfur granules is done by spreading out the pus in a petridish containing sterile saline. The granules are approximately 1 mm in diameter and can be seen by the naked eye as yellowish-white, spherical or cauliflower-like particles. Sometimes the granules can be as large as 2.5mm. 

 Microscopy: Grains should be washed several times in saline and crushed between two slides, stained with 1% methylene-blue solution, and examined microscopically for features characteristic of actinomycetes. A clump of filamentous actinomycete microcolonies surrounded by polymorphonuclear neutrophils can be observed. Gram stain shows gram-positive, intertwined branching filaments, with radially arranged, peripheral branches. Histopathologic sections reveal suppurative and granulomatous inflammatory reaction, connective tissue proliferation, and the presence of sulfur granules.

Culture: Prompt transport of the specimens to the microbiology laboratory is necessary for optimal isolation of actinomycete organisms, preferably in an anaerobic transport medium. The granules are cultured on media like Schaelder blood agar with or without gentamicin, Columbia Nalidixic acid agar or chopped meat glucose broth and incubated anaerobically at 37oC for 48 hours or longer. The isolation and definitive identification of actinomycetes may require 2-3 weeks. A.israelii produces minute spider-like colony at 48 hours, and by 10 days hard, lobulated colony resembling "molar tooth' develops.

Molecular techniques: Nucleic acid probes and polymerase chain reaction (PCR) methods are being developed for more rapid identification.
Serology: Agglutinating, precipitating and complement fixing antibodies have been demonstrated in patients, but are not reliable as there is no consistency.

Treatment: Penicillin G is the drug of choice for treating an infection caused by actinomycetes. Most patients respond to prolonged courses of antibacterial therapy. Extensive surgical procedures may sometimes be required.