MELIOIDOSIS (melioidosis; grech, melis sap + eidos a look + — osis; synonym false sap) — the infectious disease from group of zoonoz proceeding at the person as a septicaemia with damage of internals and formation in them of the septic centers.
In 1911 the English medical officer A. Whitmore during the opening of corpses of people in Rangoon (Burma) found. and in 1912 sovm, with Krishnasvami (Page S. Krishnaswami) allocated the infestant called by it Bacillus pseudomallei. In 1913 Mr. W. Fletcher in Kuala-
Lumpur and in 1917 Mr. Stanton (Th. And. Stanton) in Saigon allocated from corpses of people, laboratory and wildings the microbe identical described by A. Whitmore. The name «melioidosis» was accepted on the IV congress of the Far East association of tropical medicine in 1921
occurs At the person M. in the form of sporadic diseases, hl. obr. in a tropical zone, a thicket in the countries of the Indochina peninsula. The disease was registered also in other districts of Southeast and Southern Asia, in Northern Australia, Central America. In the same districts, and also in the nek-ry countries of Africa (Nigeria, Upper Volta), on the island of Madagascar, the Antilles islands M.'s diseases house and wildings, sometimes in the form of an epizooty are revealed. After World War II of a disease hron, forms M. appeared in the USA, England, France, the Netherlands among the persons which came back from Southeast Asia. There are messages on M.'s case with damage of lungs in Iran. In the USSR of diseases M. is not registered.
the Activator M. — Pseudomonas pseudomallei (Whitmore, 1913; Haynes, 1957) belongs to the class Schizomycetes, the Pseudomonadaceae family, on morfol, and biol, is close to properties to the activator of a sap (Pseudomonas mallei) and a pyocyanic stick (Pseudomonas aeruginosa) that is confirmed with experiments on hybridization of their in vitro DNA.
P. pseudomallei — a bacterium with the rounded-off ends of 3,0 in size — 6,0 X 0,3 — 0,6 microns, located in smears odinochno, short chains or small groups. Unlike the activator of a sap it is mobile; has several thin flagellums, but young cells can be monotrikha. The gramotritsatelna is well painted with all aniline dyes, often painted bipolyarno in the form of a safety pin that is connected with accumulation at poles of a cell of grains poly-and beta and oil to - you. The dispute does not form. Facultative aerobe; without oxygen can grow in the environments containing nitrates; it is capable to synthesize all necessary metabolites from simple connections, does not need growth factors. At pH of the environment within 5,6 — 8,5 (with an optimum 6,8 — 7,5) well grows on mediums, including on the synthetic, containing in quality sources of nitrogen and carbon ammonium sulfate and glucose or other hydrocarbon, acetate or sodium citrate. Can breed even in mains water. The temperature optimum of growth 37 °, but breeds also at t ° 20 ° and 41 °.
At crops for 3 — 5% the glyceric agar in 24 hours forms small convex colonies. In 48 hours the phenomena of dissociation are found, and colonies of a R-form with a crumpled surface are characteristic. Except them colonies of a S-form with equal, slightly convex surface, large mucous colonies (M-form) and a set of intermediate forms of colonies are formed. All of them possess the peculiar smell (reminding a smell of a mold) and get cream, orange or yellowy-brown coloring. At crops on broth there is uniform opacification of the environment and usually education on its surface of a thick folded film. On a blood agar (with rabbit erythrocytes) hemolysis is observed.
All strains recover nitrates in nitrites (in anaerobic conditions — with gas generation), reduce methylene blue, have katalazny and peroksidazny activity. Svezhevydelenny strains ferment with education to - you many carbohydrates and alcohols, including glucose, mannose, a maltose, a mannitol, a galactose, fructose, trehalose, dulcite. They possess the proteolytic enzymes liquefying to gelatin and the turned Leffler's serum. The indole is not formed; data on formation of hydrogen sulfide are contradictory.
From cells of the activator M. thermolabile flagellar N-antigen, the thermostable shell K-antigen collapsing salt to - that, thermostable and steady to salt to - those somatic O-antigen, the low-studied somatic R-antigen, and also the mucous M-antigen appearing in old cultures at a lysis of microbes are emitted. N - and M-antigens are specific to the activator M., and About - and K-antigens are the general with a stick of a sap. An obol ochechny and somatic antigens represent difficult antigenic complexes. Virulence and toxicity of the activator connect with K-antigen; drugs of a cell wall of the activator M. cause a necrosis of skin with formation of infiltrates like granulomas.
The activator M. forms two species-specific thermolabile exotoxins having antigenic properties, one of to-rykh causes hemorrhagic - necrotic defeats, and the second causes death a lab. animals (Guinea pigs, rabbits) without noticeable damage of fabrics to an injection site.
Several specific bacteriophages, each of are revealed to-rykh lyses only limited number of strains of the activator M., and also a stick of a sap and does not lyse other microorganisms. Polyvalent melioidozny bacteriophages are offered.
Resistance of the activator M. to heating is low: at t ° 56 ° it perishes in 10 — 12 min., at t ° 70 ° — in 5 min., and at t ° 100 ° — is almost instant. Against drying and cooling it is steady, well remains in the lyophilized state. To action of antiseptic agents it is unstable; for disinfection of the objects infected with the activator M. use chloroamine and other chlorine-containing drugs, phenol, lysol and caustic soda in the concentration which are usually used in disinfection practice.
the Question of sources of an infection at M. cannot be considered as solved. Many researchers considered sources of an infection of wild rodents. This statement was based on allocation of the activator M. from spontaneously infected rats and mice, and also a susceptibility of different types of rodents to M. observed in an experiment. However infectiousness of rodents turned out the activator M. in endemic districts insignificant. Besides there are no direct proofs of infection of the person and animals from rodents, human cases at patient care are not known for animals.
It is established that animals can be involved in epizootic process wild and house (goats, sheep, pigs, cows, horses, rabbits, dogs, cats). At the same time goats quite often become long carriers of the activator M. In Australia M.'s epizooty among sheep, goats and pigs is described though the source of developing of an epizooty remained obscure. M.'s diseases pigs in Kampuchea, Vietnam are known; horses in Malaysia, on the island of Java, on the Philippine islands. Possibly, the role of a source of an infection at M. is carried out by several animal species.
There is a doubtful judgment of Redfirn (M. of S. Redfearn, 1966), Fournier (J. Fournier, 1971), etc. that P. pseudomallei, being a resident of the soil and water of districts, endemic on M., participates in a mineralization and a denitrification of the soil and for the preservation as a look does not need browning through an organism of an animal. Thus, based on this judgment, the contaminated soil and water should be carried to sources of infection of people and animals. However, proceeding from recognition of the parasitic nature of causative agents of infectious diseases of the person and animals to consider objects of the environment as a source of an infection it is epidemiologically not proved.
Infection of the person occurs preferential through the injured skin or mucous membranes at contact with water and the soil (factors of transfer), in to-rykh activators contain.
This mechanism of transfer is easily feasible during the work on rice fields, during the bathing in standing reservoirs, etc. At a research of infectiousness of the environment the activator M. in Malaysia is found in 15 — 33% of tests of water and the soil of rice fields, in 6 — 10% of tests from other sites cleared of the wood and in 1 — 4% of tests from forest districts. M. preferential adult men working at rice fields, irrigational systems in the boggy jungle, and also the military personnel who was involved in military operations in these territories got sick. At soldiers of the fr. forwarding case in Vietnam in the 50th not less than 100 diseases of M., and at an amer were observed. the soldier in the 60th — apprx. 150. Antibodies to the activator M. found in wounded by 6 times more often than at the others an amer. soldier.
Along with it also other ways of transfer of activators at M are not excluded. The aspiration way of infection at hit is in some cases observed in easy for dust. Damage of lungs at an amer. soldiers in Vietnam sometimes were connected with inhalation of the infected hydrosol created by air flows from helicopters during the flight at small height over rice fields.
Infection of the person M. and is not excluded an alimentary way at consumption of the infected water or food. The opinion on the leading role of an alimentary way of infection of M. did not receive epidemiol, and experimental confirmation and, apparently, this way is not of great importance; such infection is possible only at hit with food of massive doses of the activator.
In an experiment the possibility of preservation and reproduction of a microbe in an organism of a flea of Xenopsilla cheopis and a mosquito of Aedes aegypti, and also transfer to his healthy animals is shown, however the data confirming transmissible transfer of M. under natural conditions are not available.
In endemic districts of people contacts to the activator M., apparently, quite often, however sensitivity of the person to it is low, clinically expressed forms of a disease meet seldom, hl. obr. at persons with the lowered resistance or at massive infection. At mass inspection of recruits in Malaya antibodies to the activator M. were found in 10%, and at living in districts of cultivation of rice — in 20%.
Cases of infection of M. from the person are not described.
the Pathogeny is studied insufficiently. After implementation of the activator M. in an organism it quickly gets into blood, intoxication develops and there are multiple centers of an inflammation and a necrosis in various bodies and fabrics. Wedge, disease is defined by degree of a septicaemia and a septicopyemia, and also localization of focal defeats. At rather high body resistance and a small dose of the activator process can be isolated in the few or in any one body, a thicket in lungs. In some cases the expressed septicopyemia (see. Sepsis ) no, and local the wedge, manifestations arise in months and years of a latent current, and the aggravation of process is connected with any other disease, surgery or other factors weakening an organism.
Patomorfol. the picture at M. differs from the changes arising at other septic diseases a little. The persons who died in a septicemic phase have diseases, find a plethora and dot hemorrhages in skin, mucous and serous membranes. Sometimes in lungs, is more rare in a liver and a spleen multiple small ochazhka of a necrosis manage to be formed, in smears from to-rykh during the coloring across Gram or across Gimza the activator in the form of a short bipolar stick usually is found. At a septicopyemia such centers in various bodies and fabrics turn into the small abscesses surrounded with a zone of a hyperemia and accurately delimited from surrounding fabrics. In walls of abscesses and hillocks there is a large amount of polymorphonuclear leukocytes, and sometimes and histiocytes. In lungs process proceeds in the form of pneumonia, and abscesses can be very large. Multiple abscesses often find in a liver, a spleen and limf, nodes, is more rare in kidneys, a brain, heart, in bone, muscular and fatty fabrics. Abscesses increase, sometimes to the considerable sizes, contain slivkoobrazny or yellowish pus. Damages of intestines with formation of erosion and ulcers are sometimes observed. Unlike the changes caused by a pyocyanic stick at M. there is no noticeable defeat of a vascular wall.
At hron, slow forms of a disease find the same elements separately located in lungs, hypodermic cellulose, limf, nodes, muscles, bones or other bodies. At the same time on the periphery of suppurative focuses the granulomas consisting generally of epithelial and colossal cells, a large number of monocytes and surrounded with a zone of fibrosis are quite often formed. Such abscesses of a star-shaped form remind defeats at a tularemia, and the caseous centers difficult of an otlichima from tubercular. However at crops of contents of abscesses on mediums, as a rule, it is possible to find the activator * diseases.
Immunity at M. is studied a little. It is known that serol, reactions remain positive after a wedge, recovery or after a subclinical form of a disease for a long time.
A clinical picture
On a wedge, to a current distinguish acute, subacute and hron. M. Fournier and Shambon (J. Fournier, L. Chambon, 1958) on kliniko-morfol, to signs subdivide M. into septicemic, septicopyemic and local forms.
Duration of an incubation interval at M. is definitely not established. In a case lab. M.'s infections, observed in Canada, it made 4 days, at infections, are connected *, with a fighting injury — 5 — 10 days. Cases of latent infection when the incubation interval lasted for months and years are described.
Acute M. is characterized by bystry rise in temperature to 40 — 40,5 °, head, muscular, often pleural pains, sometimes the abdominal pains which are followed by vomiting, jaundice and a diarrhea. Cough with a bloody and mucous phlegm, later — with department of dense yellowish or greenish pus is often observed. In lungs quite often there are large pneumonic centers. Note tachycardia, arrhythmia, small increase in a liver and spleen. Increase limf a bit later, nodes, are more often cervical and axillary. There comes the loss of consciousness, is frequent with nonsense and the meningeal phenomena. On skin the erythema of various type, a plentiful rash of pustules and hemorrhagic bubbles can appear. In blood — the expressed neutrophylic leukocytosis, the raised ROE. If the patient does not perish from a collapse in the first days of a disease, the described picture is supplemented with developing of abscesses in various fabrics and bodies, a thicket in lungs.
Subacute M. differs in less expressed intoxication, existence of short remissions with noticeable decrease in body temperature. A condition of the patient usually heavy, the bystry lose of weight of a body is characteristic. Into the forefront suppurative processes, usually with formation of multiple abscesses in internals, muscles, hypodermic cellulose act. The purulent inflammation of serous cavities (an empyema, peritonitis, arthritis), pyelonephritis, cystitis, osteomyelitis of various localization develops. Purulent meningitis and encephalitis, napr, the skulls tied with purulent damage of bones are sometimes observed.
At hron. The m is noted existence of slow suppurative processes in one or few bodies with formation of not healing fistulas, ulcers and natechnik. Standard temperature or slightly raised. Process can last for months and years, M.'s case in Australia proceeding 24 years is described.
Not distinguished hron. The m in the form of small primary center can at disturbance of body resistance, napr, at a burn, become aggravated, cause a septicaemia or a septicopyemia with a rapid heavy current and a lethal outcome. Exceptional cases of similar transformation and clinically expressed local hron are known.
Authors allocate to M. Nek-rye in a separate form the pulmonary M. which is not followed by defeat of other bodies. Existence and the abortal form M. proceeding in the form of a short feverish disease is supposed, later to-rogo in blood antibodies to the activator M.
the Diagnosis on a basis a wedge are found, pictures of a disease it is extremely difficult. Authentically M.'s diagnosis can be established only on the basis a lab. researches. It is necessary to consider also stay of the diseased in districts, endemic on M.
The basic and the most reliable diagnostic method of M. is bacterial, a blood analysis, phlegms, pus, urine, slime from a nasopharynx and other allocations; in Calais the activator is found seldom. The intake of material from the patient, his delivery in laboratory and a research is conducted, as at quarantine diseases. Material is mikroskopirut and sowed on mediums. For allocation of the activator M. from objects of the environment or from the materials received from patients as the elective environment use a beef-extract agar from 3 — 5% of glycerin and a crystal violet or other dye — inhibitor of growth of gram-negative bacteria, and also Levin's circles and the IAC Horse tram. As the highly effective elective environment L. A. Ryapis and D. T. Shiryaev (1974) recommend to 2% an agar from 0,02% of magnesium sulfate and 0,1% of sulfite of sodium, add beta alanine to final concentration of 0,03 M. to Krom and Neomycinum (25 mkg/ml).
For release of pure growth of the activator use also infection with the studied material of Guinea pigs or golden hamsters with crops of bodies of the fallen animals. For identification of a microbe in this case an important role is played by development in the males of a scrotal phenomenon infected intraperitoneally on 2 — the 3rd day after infection.
Identification of the activator M. is made on its complex morfol., cultural, biochemical, antigenic and pathogenic properties. From the activator of a sap it is distinguished on mobility and active growth, and from a pyocyanic stick — on antigenic properties and lack of formation of a water-soluble green or blue-green pigment. As the emergency approximate ways of identification use luminescent serol. a research by means of specific fluorescent serums, and also an agglutination test with specific erythrocyte diagnoses mind of ohms. However these methods do not allow to differentiate activators M. and a sap.
Serol, diagnostic methods play a supporting role. The agglutination test is a little specific, is observed at salmonelloses and even at healthy people, diagnostic value has only increase of an antiserum capacity at a numerous research of serum in the course of a disease.
Reaction indirect is more widely applied to diagnosis hemagglutinations (see) with erythrocytes of a ram, sensibilized polisakharidny antigen of the activator, diagnostic value has a caption 1: 40. RSK is less sensitive, at a cut the caption 1 is diagnostic: 20, but if at a sapa of RSK it is always positive, then M.'s cases from negative RSK are known (see. Reaction of binding complement ).
The differential diagnosis
Various options of a current of acute M. are similar with pulmonary or bubonic plague (see), sapy (see), cholera (see), smallpox (see. Smallpox natural ), typhoid (see), miliary tuberculosis (see), and hron, forms of a disease — with tuberculosis, actinomycosis (see), hron. staphylococcal infection (see), mycoses (see), etc.
At an acute and subacute form M. appoint parenteral administration of antibiotics in max. shpalny doses. Levomycetinum is effective (chloramphenicol especially in combination with drugs of a tetracycline row and streptocides (Norsulfazolum, Sulfadimezinum). In some cases with success applied Kanamycinum. As a rule, penicillin, streptomycin, erythromycin and Neomycinum are not effective. The maximum doses of drugs enter before subsiding of the acute phenomena then treatment by reduced doses is continued by not less than 30 days in order to avoid a recurrence. Oral administration of antibiotics and streptocides continue within 3 — 6 months, and upon transition of a disease in hron, a form — longer. Emergence of a recurrence indicates changes of the applied combination of drugs the need. According to features of disease treatment by antibiotics and streptocides is supplemented with use of detoksitsiruyushchy, regidratiruyushchy and symptomatic means.
At hron, forms M. treatment by antibiotics and streptocides is combined with different types of an operative measure, up to lobectomies (see) in case of a pulmonary form of a disease with formation of the large centers of disintegration. The immunotherapy (in particular, specific horse gamma-globulin) is in a stage of development.
The forecast at acute and subacute M. adverse, especially if, despite treatment, disease severity in the first days does not decrease.
The forecast is more favorable at hron., especially local pulmonary M.
the Main action in M.'s prevention — identification of sick animals by means of allergy diagnostic test (as allergen the filtrate of 5 weeks bouillon culture of the activator M. — uitmorin is used). Sick animals are isolated and treated or destroyed. Burial of corpses of animals is made on specially allotted dry sublime places. Much attention is paid to the maintenance of livestock farms, timely cleaning and disinfecting of manure. The personnel which are looking after the cattle are provided with overalls and footwear, disinfectants. The important role belongs to increase a dignity. cultures of the population, especially personnel of cattle breeding farms.
In settlements and on livestock farms the constant is carried out deratization (see).
Prevention of production wounds, grazes, attritions at the persons working at rice fields, water meadows, etc. has serious value.
Measures for protection of sources of water supply against penetration of rodents, the use are necessary for drink only of a decontaminated water, boiling of milk, strict veterinary supervision behind slaughter of the cattle.
Sick people are hospitalized surely. Write out from to lay down. institutions only after double bacterial, inspections, at Krom do not find the activator. The persons communicating with the patient before hospitalization are exposed to medical observation within 15 days.
The territory of the USSR is not endemic according to M., however the possibility of delivery of sick domestic or exotic animals is not excluded from endemic districts. Such animals it is necessary to reveal and take timely measures for the prevention of pollution by manure of surrounding - Wednesdays.
Specific prevention of M. is not developed.
Bibliography: Kovalyov G. K. Results of 60 years' studying of a melioidosis, Zhurn, mikr., epid, and immun., No. 2, page 21, No. 3, page 15, 1976; it, Melioidosis, Owls. medical, jvft 5, page 88, 1978, bibliogr.; To r and m and N-skiyv. And. and Naletova JI. E. Geografiya of a melioidosis, in book: Medical geography, under the editorship of A. D. Lebedev, t. 5, page 5, M., 1972, bibliogr.; A melioidosis, under the editorship of D. T. Shiryaeva, etc., M., 1976, bibliogr.; Fournier J. Epidemiologie de la mSlioidose, Bull. Inst. Pasteur, t. 69, p. 385, 1971; Howe C., S'a mp at h A. S p o t n i t z M. The pseudomallei group, J. infect. Dis., v. 124, p. 598, 1971, bibliogr.; P i g g o 11 J. A. a, H o with h h o 1-zer L. Human melioidosis, Arch. Path., v. 90, p. 101, 1970; H e df earn M. S. P an of 1 1 e r o n i N. J. a. S t a n i e r R. Y. A comparative study of Pseudomonas pseudomallei and Bacillus mallei, J. gen. Microbiol., v. 43, p. 293, 1966; Stanton A. T. a. Fletcher W. Melioidosis, L., 1932; Z i e r d t of Page H. a. M a r s h N.N. of Identification of Pseudomonas pseudomallei, Amer. J. clin. Path., v. 55, p. 596, 1971.
I. M. Chernyak.