Nocardiosis

Description:

Nocardiosis (synonyms: streptotrichosis, кладотрихоз, atypical actinomycosis; Nocardiose - is mute.; nocardiose - fr.)  - the mycosis which is characterized by the long progressing current with frequent damage of lungs, the central nervous system. Lethal outcomes are frequent.

Nocardiosis reasons:

The infections caused by Nocardia spp. happen both at people, and at animals. Distinctions in an etiology, clinical symptomatology, treatment and the forecast allow to distinguish two subgroups of diseases, namely: nocardiosis of sensu stricto and aktinomitsetoma. The last which can be also called "actinomycotic mycetomas" are clinically well certain nosological form of a disease with a heterogeneous etiology which causes not only Nocardia, but also and Actinomadura and Streptomyces spp.

Definition of a nocardiosis though, first of all, etiological, is at the same time both clinical and pathological. His potential causal agents - Nocardia asteroides, Nocardia farcinica, Nocardia nova, Nocardia brasiliensis, Nocardia pseudobrasiliensis, Nocardia otitidiscaviarum and Nocardia transvalensis. Considerable doubts remain rather taxonomical status of N. asteroides, N. farcinica and N. nova that influences their identification. Until recently all these microorganisms were included in N. asteroides, but then separated from N. asteroides sensu stricto by taxonomical and molecular methods. Thus, it is still difficult to estimate degree to which by N. farcinica and N. nova are involved in infections at the person though, at least, the last can be reliably identified.

Pathogeny:

Nokardialny defeats can be purulent or granulematozny or that and others together that does their histopathological manifestations very variable. Abscesses and pure granulomas can be found, but the answer of an organism mixed becomes more often. Formation of granules - does not characterize any any type of a nocardiosis, but is usual for an aktinomitsetoma.

As pathogenic nokardiya vegetirut mainly in the environment, a nocardiosis at the person always of an exogenous origin. Assumptions that noninvasive colonization by nokardiya of respiratory tracts can be the cause of endogenous infections, are not convincing. Allocation of pathogenic Nocardia spp. from a phlegm or a bronchial secret in the absence of symptoms of a pulmonary disease points to short-term contamination or a subclinical infection rather, than to long colonization.

Pathogenicity of various Nocardia spp., mentioned above, has some certain distinctions in dependence on a look. Pulmonary, system, the nocardiosis of TsNS and an extrapulmonary nocardiosis in the prevailing number of cases are caused by N. asteroides, N. farcinica, is more rare - N. pseudobrasiliensis and, only sometimes, N. nova, N. brasiliensis, N. otitidiscaviarum and N. transvalensis.

There is no full clarity of rather clinical importance of N. farcinica. In the review of literature of Beaman and Beaman (1994) found only 13 cases of the infection caused by N. farcinica from 1050 cases while Schaal and Lee (1992) revealed 60,3% nokardialny infections, the caused this microorganism. It is undoubted that problems with identification of the activator could influence the results received by Beaman and Beaman (1994) though regional distinctions also can be responsible for such discrepancy of results.

Superficial skin and hypodermic infections were caused mainly N. brasiliensis, also as N. otitidiscaviarum and N. transvalensis. These infections can be also caused sometimes by N. asteroides, N. farcinica and N. nova. Nocardia brevicatena was isolated from the respiratory treatise, however its etiological role in infections at the person was not established.

Immune response at a nocardiosis
The relations a parasite owner at nokardialny infections are considered by Beaman and Beaman (1994). Attempts were made to find antibodies to Nocardia spp. for the purpose of possible use for the diagnostic purposes. There is very few information of rather diagnostic value of these tests. Kjelstrom and Beaman (1993) investigated possibilities of various serological tests for diagnosis of a nokardialny infection. These researches assumed existence of correlation between synthesis of antibodies and a nokardialny infection, under a condition if clinical and other factors were also taken into account.

Researches on animals showed that macrophages, T-cells, and cellular immunity play an important role in body resistance of a nokardialny infection. Macrophages englobe nokardialny cells and, depending on virulence of a specific look, the majority of the absorbed organisms kill. A part of less virulent strains can survive in the form of L-forms in a phagocyte while more virulent strains breed in a macrophage, and nokardialny threads can burgeon through a cell membrane. Macrophages can or activate T lymphocytes and stimulate a cellular immune response, or can be directly to carry out a killing of nokardiya.

Nocardiosis symptoms:

Except an aktinomitsetoma, define 5 main forms of a nocardiosis (Beaman and Beaman 1994):
1. Pulmonary nocardiosis
2. The system nocardiosis involving two or the bigger number of bodies
3. TsNS nocardiosis
4. Extrapulmonary nocardiosis
5. Skin and limfokozhny nocardiosis.

This division is more detailed, than the offered Schaal and Beaman in 1984, but justified from the clinical, medical and predictive point of view.

Pulmonary nocardiosis
Nokardialny cells in connection with their natural dwelling in the soil or plant material can get to air in the form of fragments of a mycelium or contain in parts of dust. Thus, pulmonary infections arise, mainly, after inhalation of these infected parts. The exceptional cases of a pulmonary norkardioz connected with hematogenous distribution from an oral cavity or the gastrointestinal treatise after consumption of the contaminated food stuffs, or after accidental introduction (for example, addicts) directly in a blood channel, or implementations of the activator in fabric owing to an injury are reported. Inhalation of reproductive nokardialny cells not always leads to a disease. Except their passing presence at respiratory tracts soon after inhalation of the contaminated dust, it is necessary that pathogenic nokardiya could colonize or infect subclinically respiratory tracts. Remains not clear as often there is such colonization or subclinical infection.

Except system immunosuppression, damage of local protective mechanisms of lungs which include can contribute to development of a nocardiosis: chronic bronchitis and emphysema of lungs, bronchial asthma, bronchiectasias and an alveolar proteinosis, however invasive process in lungs can also happen at patients without local or system defects of protection. Clinical ideas of a nocardiosis of lungs are very variable. The pneumonia which is often connected with formation of abscess or a cavity is most often observed subacute or chronic, quite often necrotic. At patients with the expressed immunosuppression the disease sometimes is shown as an acute fulminant necrotic pneumonitis which can lead to death before the diagnosis is established. The pulmonary nocardiosis can be also presented as slowly shown separate or multiple pulmonary small knots or parietal pneumonia with an empyema. Usual complications include: pleural exudate, empyema, pericardis, mediastinitis, obstruction of an upper vena cava and, sometimes, abscesses of a chest wall. Hematogenous distribution is characteristic of such cases that can conduct to a system nocardiosis, including a nocardiosis of the central nervous system.

Patients with a nocardiosis of lungs usually have the following symptoms: fever, night sweats, loss in weight, productive cough and, sometimes, a pneumorrhagia. To a disease the pleura empyema can precede or accompany, in these cases pleural pains can be the main complaint. Data of radiological inspection are usually not specific and include limited infiltrates which are shown as wedge-shaped shadows in the right average zone, small knots, formation of cavities within small knots or infiltrates, a pleural exudate and increase in radical lymph nodes. Multiple small knots, abscesses, miliary defeats, diffusion intersticial infiltration and subpleural plaques meet much less often.

System nocardiosis
On any site of defeat the nokardialny infection can get to a blood stream and metastasize in other bodies. Sometimes, microorganisms can be transferred with blood after an injury the contaminated materials like thorns, wooden splinters and bullets, and also owing to accidental hit from the infected syringes or needles at addicts, or after stings of insects or animals. By definition, the system, or disseminated nocardiosis is diagnosed in cases if damages are present at two or more sites of an organism. Any anatomic education, however TsNS and, especially, a brain - the extra pulmonary sites which are most often involved in pathological can be struck. The brain nocardiosis, in the form of specific nokardialny brain abscess, is the important reason of volume formations of a brain. Usual places to which the infection can also extend: kidneys, spleen, liver, hypodermic fabrics and eyes. In an eye the retina usually is surprised. Very seldom nokardialny metastasises find in bones, joints, heart or skin. Formation of abscess - usual manifestation disseminated a nocardiosis. Thus, symptoms of a disease depend on the size and location of abscess and pain because of an inflammation and the shift of the next fabrics.

Nocardiosis of the central nervous system (CNS)
Nokardialny damages of the central nervous system - one of the most frequent localizations at system forms and usually follows a pulmonary nocardiosis. Among 1050 cases described in literature analyzed by Beaman and Beaman (1994), TsNS was involved in 22,7% of all observations, and also in 44% of cases at patients with the disseminated nocardiosis. In 38,2% cases of a nocardiosis of TsNS of symptoms of an infection in any other place were not. Therefore the nocardiosis of TsNS can be considered and as primary infection. Besides, 42% of patients were previously healthy individuals without the obvious contributing factors. Therefore Nocardia spp. are primary pathogens of TsNS and especially a brain. The beginning of a nocardiosis of TsNS often artful as even big damages can not cause the expressed symptomatology. Such defeats are usually presented as abscesses, more rare as granulomas and only seldom or never - as meningitis. Abscesses of a brain and granuloma can sharply proceed, with bystry distribution, but usually the disease progresses slowly within months by years. As TsNS infections in itself often are not followed by fever or a leukocytosis, often treat them as tumors. Symptoms depend on localization of damages. Sometimes, only the spinal cord is surprised.

Extrapulmonary nocardiosis
Whether the question is an extrapulmonary nocardiosis the same infection as skin, hypodermic and limfokozhny or as defeats of TsNS or it has to be considered in separate category as Beaman and Beaman (1994) is offered, remains disputable. Extra pulmonary infections can be found in bones, eyes, heart, joints and kidneys. Nokardialny damages of an eye can happen to involvement of a retina during the disseminated nocardiosis. Primary eye infections usually follow an injury or, more rare, surgical intervention with pollution by pathogenic nokardiya, and conduct to a keratitis and further, finally, - to an entophthalmia. In an inadequate way the sterilized soft contact lenses - less usual source of exogenous nokardialny damages of eyes. The Nokardialny keratitis can remind noninfectious inflammatory diseases of eyes that sometimes conducts to serious complications if to appoint corticosteroids.

Nokardialny infections of joints are presented as septic arthritis which identification frequency constantly increases. The same treats a nokardialny pericardis and an endocarditis. Cases of nokardialny endocarditises after prosthetics of the aortal valve which were successfully cured imipenemy, amikacin and operation on replacement of the valve were described.

Limited skin, hypodermic and limfokozhny nocardiosis
Except involvement of skin and hypodermic fabrics during the disseminated nocardiosis, it is also possible to face primary skin and hypodermic nokardialny defeats. They usually follow implementation of pathogenic nokardiya in skin through the chipped wounds, stings of insects or dogs, scratches put with animals. As Nocardia spp. usually is present at the soil, such infections have to meet, in principle, rather often, however the skin nocardiosis is rare that indicates that these infections often proceed subclinically or do not come to light as can pass without treatment and remind other skin infections.

Primary response to implementation of pathogenic nokardiya in skin - a panniculitis or a pyoderma from which abscess can develop. Pustules or slowly extending small knots can be also observed. All these manifestations resemble the infections caused by others purulent bacteria except that nokardialny infections tend to proceed more without serious consequences. Nokardiya can extend in lymphatic ways to regional lymph nodes with a characteristic clinical picture of a limfokozhny nocardiosis. Almost identical syndrome can be observed at defeat by a mushroom of Sporothrix schenckii (sporotrichosis) in this connection limfokozhny nokardialny infections are often mentioned as a sporotrikhoidny nocardiosis.

Diagnosis:

The reliable diagnosis of a nocardiosis is possible only allocation of the causal agent from a patmaterial, including a phlegm, bronchial washouts, exudate, pus, cerebrospinal liquid, blood, urine and materials of autopsy or a biopsy. Though pathogenic nokardiya are quite steady against external influences, materials for a research have to be transported in laboratory quickly because nokardiya which grow slowly usually grow with kontaminiruyushchy bacteria. Cooling is not desirable because some types of Nocardia do not transfer low temperatures.

When coloring, for example, across Gram or silver impregnation, microscopic examination of a phlegm, pus or samples of fabric can find the filamentous branching bacteriums. The microscopy of nokardiya has no distinctions with fermentative and aerobic actinomycetes. The specification is possible only by cultural methods, and, in the long term, - molecular (PTsR).

For blood, cerebrospinal liquid and empyemic exudate for Nocardia spp allocation. any general environment of incubation approaches at a temperature of 36+-1 °C. Solid nutrient mediums have to be transparent, like brain - a cordial agar so that growth could be observed microscopically at early stages. For a research of the patmaterial which is usually containing inborn microflora of mucous membranes (for example, phlegms, a bronchial secret, urine, autopsy material) the selection environments, with the purpose to reduce risk of overgrowing by kontaminiruyushchy microorganisms of a slow-growing nokardiya have to be used. Identification of nokardiya to a look demands hemotaksonomichesky, carbon and hydrolytic tests. Reliable identification of N. asteroides sensu stricto, N. farcinica and N. nova is especially difficult because they are divided into many phenotypical signs. In sensitivity to antibiotics recognition of these versions can facilitate distinctions.

Though attempts of creation serological diagnostic tests for recognition of nokardialny infections, however were made in one case use any the separate or combined tests did not yield satisfactory results. Also attempts to use research DNA for bystry identification of the suspect of N.asteroides isolates were made. The diagnostic value of such researches is also limited as N. asteroides - a heterogeneous version which demands big group of researches to identify all her members. The same treats also the PTsR methods.

Treatment of a nocardiosis:

The choice of specific medicines for treatment of a nocardiosis remains disputable because of problems of a research of sensitivity of these microorganisms and a lack of controlled clinical trials on this matter. The available recommendations are usually based on limited number of observations. However the data obtained by in vitro and on experimental animals with N. asteroides are directly applicable also to human infections. Pathogenic nokardiya showed significant differences in sensitivity and, besides, it is necessary to consider possible geographical distinctions in a susceptibility; that, apparently, N. farcinica and N. nova matters for N. asteroides. As the exception, the European samples of N. asteroides and N. farcinica are sensitive to streptocides or Biseptolum. Out of this region, only N. brasiliensis is usually susceptible to these drugs.

Therapy of the choice for the nocardioses caused by N. asteroides and N. farcinica - high doses of an imipenem and amikacin. The daily dose of an imipenem should not be less, than 4 g, as well as for amikacin, and these doses have to be based on concentration of drug in blood serum. Some types of N. asteroides are also sensitive to amoxicillin plus clavulanic acid and this combination can be used when the culture is badly sensitive to imipeny. For N. brasiliensis, N. otitidiscaviarum and N. transvalensis such therapy is usually not effective because of resistance either to imipeny or to a complex amoxicillin plus clavulanic acid or to that and others. Nevertheless, resistance to amikacin, was observed at pathogenic nokardiya quite seldom therefore this drug должнен to enter as a therapy component. Streptocides, Biseptolum and tetracyclines, especially minocycline, are also effective drugs against these infections. It is necessary to take however into account that treatment by streptocides if it in general is effective, can demand 12 months or more at allocation of N. asteroides and N. farcinica while treatment imipenemy or a complex usually leads amoxicillin-clavulanic acid plus amikacin to improvement in limits of week and recovery within 4-6 weeks. If after antimicrobic therapy there is recurrence, especially in lungs or at brain abscess, or the valve endocarditis connected with prosthetics the question of operational treatment has to be considered.