Histoplasmosis

Aetiology. The originator - Histoplasma capsulatum - the dimorphous mushroom existing in histic and cultural forms. The histic form settles down in cells of organs of reticuloendothelial system (a liver, a lien, lymph nodes). Under the form and the dimensions (2-4 microns) this microorganism reminds a leishmania or a toxoplasma. The mycelium form of a mushroom never meets in tissues. It well educes on nutrient mediums at temperature more low 30 °. Histoplasma capsulatums in both phases are pathogenic for white mice, rats, Guinea pigs, golden hamsters, dogs. A mushroom it is long remains in wet bedrock (6 weeks) and in water. Quickly perishes under the influence of various disinfectant preparations.

Epidemiology. The disease-producing factor remains in bedrock. In contamination (infestation) of bedrock has certain value mushroom abjection by the infected animals and auks (bats, cats, dogs, hens, grackles, etc.). The becoming infected of humans descends air-dust by. Cases of infestation of the human from sick humans and animals it was not observed.

The histoplasmosis of eurysynusic Africa in the various countries and Americas, meets also in Europe and Asia, histoplasmosis single instances are described in our country, brought in cases are possible also. The most infected are the ranges located from 45 "to 30" to the north. The important role in a histoplasmosis epidemiology is played by bedrock. In rains Histoplasma propagates in bedrock. One colony of a mushroom in diameter of 2,5 sm can carry millions spores. After the terminal of the season of rains of spore dissipate in an external environment. Infestation descends at an aspiration of spores, in particular at carrying out of a different sort of excavations (pawing of tranches, building etc.). The infection contamination from sick humans is not transferred to the healthy even at long close contacts.

Pathogenesis. Infection atriums is a respiratory organs is more often. Disputes of a mushroom with a dust get to bronchuses and alveoluses, there they turn to parasitic yeast-like forms, take root into tissues and cause occurrence of the primary pulmonary locus. With a current of a lymph the originator inpours into regional lymph nodes, causing in them inflammatory process. Mushroom presence in a tissue causes formation of granulomatous process which is authorised a necrosis, an ulceration or a petrification of a pulmonary tissue and lymph nodes, is rarer abscessing. This form reminds a primary pulmonary tuberculosis. Antigens of Histoplasma capsulatums inpour into the general circle of a circulation and lead to allergic rearrangement of an organism (that is taped by an intracutaneous test with a histoplasmin) and development of specific antibodies. On it process can end, not giving the expressed semiology, sometimes process proceeds in the form of the inapparent form. In other cases there comes a hematogenous dissimination of a mushroom on all organism with a lesion of many organs. Process quickly progresses and often leads to a lethal outcome. In occurrence of the similar form the great value has a condition of immune system. Such flow, as a rule, is observed at a HIV-infected of persons.

Symptoms and flow. The incubation interval lasts from 4 till 30 days (more often 7-14 days). The more shortly the incubation interval, the proceeds disease more hardly. On clinical flow excrete following forms:

1. An acute histoplasmosis of lungs:
   • The asymptomatic (inapparent) form
   • Clinically expressed forms (easy, moderately severe, serious)
2. A chronic progressing (cavernous) histoplasmosis of lungs
3. An acute disseminated histoplasmosis (benign, progressing)
4. A chronic disseminated histoplasmosis (with a lesion of mucosas and skins)

More often there is an acute histoplasmosis of lungs that is caused by an aerogenic becoming infected.

Acute forms of a pulmonary histoplasmosis can proceed asymptomatically and to be found only at statement of an intracutaneous test with a histoplasmin, on positive takes of serological tests, sometimes on petrificates in easy and radical lymph nodes. At easy forms which prevail, the state of health of patients remains good, quite often they continue to work, the fever is absent or happens short-term (3-4 days), and the general duration of treatment of 2-3 weeks. At a X-ray inspection tap intensifying of a drawing and augmentation of a shade of roots of lungs, only at separate patients are observed low-nidus shades, mainly in the inferior parts of lungs.

Serious forms of an acute histoplasmosis of lungs are characterised by the subitaneous beginning, a fast fervescence till 40-41 °. The Temperature curve of an irregular type with the big daily scope. Tremendous cold fits are replaced by a diffusive diaphoresis. Patients complain of a strong headache, delicacy, pains in muscles and bones, tussis, stethalgias. At some patients the nausea, vomiting, diarrhoeia, abdominal pains become perceptible. Duration of a fever of 2-6 weeks. In the reconvalescence season it is long the subfebrile condition, austenization, sharp depression of working capacity, a sweating is observed. These phenomena remain till 1 year. At a percussion of lungs it is possible to note some shorting of a note, at auscultation - finely nucleate wet rhonchuses, mainly in the inferior parts of lungs.

Roentgenologically tap macrofocal and middle-nidus shades in a kind of "wadded flakes” which can merge. Further infiltrates completely disappear or on their place the fibrosis and calcination locuses are formed.

At moderately severe forms clinical and radiological implications are expressed not so sharply, the fever remains about 2 weeks, and duration of hospitalisation about one month.

The chronic histoplasmosis of lungs proceeds in the form of the long progressing disease periodically giving exacerbations. The moderate fever, tussis with a sputum is observed, at a X-ray inspection caverns, a fibrosis and the plural calcinated locuses are taped.

The acute form of a disseminated histoplasmosis shows a high fever of a hectic or irregular type, repeated cold fits and a diaphoresis, the expressed symptoms of the general intoxication (a headache, muscular and articulate pains, a nausea, vomiting, the abdominal pains, accruing delicacy). On this background there are plural secondary locuses as result of a dissimination: a various sort of an exanthema (maculopapular, furuncular, hemorrhagic, it it is a lot of a type shaped or a nodulose erythema), a lymphadenopathy, a mesadenitis, liver and lien augmentation, an encephalitis or a meningocephalitis, a septic endocarditis, an ulcerative colitis, a peritonitis. Clinical and radiological changes can remind a miliary tuberculosis (at an aerogenic becoming infected).

The chronic disseminated histoplasmosis is characterised by flaccid flow, state of health of patients in the beginning satisfactory, the fever is not expressed, involving in process of a skin and mucosas is typical. Characteristic ulcers in tongue, pharynx and larynx mucosas are formed. Further the condition worsens, there is a fever of an irregular type (septic), the augmentation of a liver, a lien, all bunches of lymph nodes, a stomach lesion, an eye (chorioretinites) etc. is observed.

Features of a histoplasmosis at children of early age. The histoplasmosis can be observed at children of the first months of life (2-6 months). Disease of children is characterised by a fever (38-39 °), a liquid foamy chair with an unpleasant odour, pallor, and sometimes and moderate yellowness of integuments and mucosas, liver substantial growth (5-9 sm below a costal arch) and liens (3-5 sm below costal edge), in all cases in process are involved lungs. At a blood analysis the progressing anemisation, a leukopenia, the raised maintenance of bilirubin becomes perceptible, activity of serumal enzymes (the AlAT, the AsAT, an alkaline phosphatase, etc.) raises. In peripheric blood the poikilocytosis, an anisocytosis, a polychromatophilia, a thrombocytopenia becomes perceptible. Disease proceeds as a disseminated histoplasmosis. In all cases (prior to the beginning of antimycotic therapy) it is possible to secure Histoplasma capsulatums from blood and from an osteal brain.

Histoplasmosis at a HIV-infected of persons. Immunodefence depression is essential raises risk of a becoming infected Histoplasma capsulatums. This problem is especially actual in regions, precinctive on a histoplasmosis. In comparison with an aspergillosis and a candidiasis the histoplasmosis meets less often (at 0,5 % sick of AIDS). In precinctive districts USA this percent considerably above. The histoplasmosis at a HIV-infected proceeds as hematogenically disseminated process and is characterised by a high fever, a lymphadenopathy, liver and lien substantial growth, as constant implications tussis and infiltrates serve in lungs. At a blood analysis the leukopenia and an anaemia becomes perceptible. Proceeds hardly, even in initial stages of a HIV-infection contamination a lethality over 80 % (in the absence of therapy), at early appointment of antimycotic preparations the lethality decreases to 15 %. At sick of AIDS the lethality reaches 100 %, and even big doses Amphotericin B do not warn palindromias. Diagnostics is at a loss negative takes as intracutaneous test with a histoplasmin, and serological tests. In the presence of a histoplasmosis (especially disseminated forms) the patient should be checked necessarily on a HIV-infection contamination.

The diagnosis and the differential diagnosis. Histoplasmosis recognition represents appreciable difficulties, especially in districts, not precinctive for the given disease. For diagnosis acknowledgement use abjection of the originator from a sputum, scrapings from a mucosa, bloods, punctates of abscesses, lymph nodes, a liver, liens, an osteal brain, smear microscopy, abjection of culture of a mushroom, a biological test on animals. For acknowledgement of the diagnosis of a histoplasmosis children of early age and at a HIV-infected the most informative had methods of abjection of culture from an osteal brain, blood and lungs. Much less often Histoplasma capsulatums managed to be found in tissues of lymph nodes, skins, a brain, an intestine. At diagnostics of a histoplasmosis at persons with normal immune system it is possible to use serological tests and an intracutaneous test with a histoplasmin. For detection of specific antibodies in blood serum put a complement-fixation test, precipitation tests and agglutinations of particles of the latex loaded with a histoplasmin. In a diagnostic caption are 1: 16-1: 32. It is better to carry out research dynamics, especially at acute forms of a histoplasmosis as reaction becomes positive only from 2-4 weeks of disease. Dermal assay with a histoplasmin is very simple. Introduce 0,1 ml of the allergen dissolved in the ratio 1: 1000, results consider in 24 and 48 hours. Reaction becomes positive in 3-4 weeks from the disease beginning. Hence, the fastest and authentic mean of laboratory acknowledgement of the diagnosis is abjection of culture of a mushroom.

Acute forms of a histoplasmosis are necessary for differentiating from an ornithosis, an acute bacteriemic pneumonia, Q fever, a mycoplasmosis, a tuberculosis. Chronic forms of a histoplasmosis differentiate from a tuberculosis and pulmonary forms of deep mycoses (a nocardiosis, an aspergillosis, a coccidioidomycosis). Disseminated forms of a histoplasmosis differentiate from a sepsis and a miliary tuberculosis.

Treatment. Patients easy and moderately severe forms of a histoplasmosis do not require appointment antimycotic (enough toxic) preparations. It is possible to confine a medical regimen, a high-grade food and symptomatic therapy. At serious forms of an acute histoplasmosis prescribe Amphotericinum In from calculation of mass of a body of 1000 ED/KG a day. A preparation introduce intravenously driply within 4 hours per 5 % glucose solution. For definition of individual shipping the first introduction is done of calculation of mass of a body by of 100 ED/KG. In the absence of side reactions and satisfactory shipping of an antibiotic introduce a preparation from calculation of 250 ED/KG and then gradually raise a dose to 1000 UNITS/KG the Antibiotic introduce in day or 2 times in a week. Duration of treatment of 4-8 weeks. At Amphotericinum introduction In by-effects are observed: thrombophlebites, a nausea, vomiting, muscular pains, cramps, intestinal bleedings, an anaemia, toxic lesions of nephroses.

At chronic forms the best results are given by long appointment of Amphotericinum In repeated 6-7-дневными courses in a combination to surgical treatment.

It is possible to use also Amphoglucaminum - a water-soluble preparation of Amphotericinum In, designed for intake. It is less toxic, from side reactions disturbance of functions of nephroses becomes perceptible only. Is issued in tablets on 100 000 Unit (in packaging of 10 or 40 pieces). Treatment is prescribed with 200 000 Unit by 2 times a day after meal. At good shipping the dose is raised to 500 000 Unit by 2 times a day. A course lechenija3-4 weeks. To watch a condition of nephroses. At protein appearance in urine or risings of level of a filtrate nitrogen above 30 mmol/l Amphoglucaminum cancel. At a histoplasmosis of eyes aboriginal application of the corticosteroid preparations, desensitizing therapy by means of a histoplasmin, and also a photocoagulation are shown.

From foreign preparations it is possible to use Ketoconazole. The preparation can be used at treatment of a histoplasmosis at a HIV-infected separately or in a combination to V.Iz's Amphotericinum of other preparations which were used at HIV-infected therapy, - fluconazole which prescribe on 50-100 mg a day. Prescribe antihistamine preparations, vitamins and other pathogenetic agents.

The forecast. At an acute histoplasmosis of lungs the forecast congenial, only at was rather rarely meeting serious forms process can pass in chronic and give relapses. At a chronic pulmonary histoplasmosis the lethality reached 60 % (without treatment by antimycotic antibiotics). At a combination of treatment by Amphotericinum In and surgical) treatments manage to be lowered a lethality to 10-15 %. The forecast at disseminated forms of a histoplasmosis, as a rule, the bad. At children of younger age the histoplasmosis proceeding as disseminated, gives in to therapy by Amphotericinum In (in age doses). The histoplasmosis at a HIV-infected proceeds hardly and even at treatment usually comes to an end with  destruction of the patient.

Preventive maintenance and actions in the locus. Specific preventive maintenance only is still developed. Chemoprophylaxis is ineffective. All-round prevention of a dust pollution of air in diffusion places in bedrock of Histoplasma capsulatums, preservation from an aspiration of air infested with mushrooms in premises, on excavations, in mycological laboratories, a careful decontamination of air in these laboratories Is recommended. The control over vegetative stuffs, fruit, the vegetables, the conforming processing of dusty subjects and the stuffs which have arrived from regions where this disease is extended. Danger sick of a histoplasmosis to other humans does not represent.