Autopsy findings in an outbreak of severe systemic illness in heroin users following injection site inflammation: an effect of Clostridium novyi exotoxin?

CONTEXT: An epidemic of unexplained illness among injecting drug users characterized by injection site inflammation and severe systemic toxicity occurred in Ireland and the United Kingdom from April to August 2000. One hundred eight persons became ill, and 43 persons died. In Dublin, 8 of 22 patients died. Six of the 8 fatal cases were epidemiologically linked to a source of heroin. Most had experienced local injection site lesions for 7 to 14 days before developing a rapidly fatal systemic illness characterized by hypotension, thirst, pulmonary edema, pericardial and pleural effusions, and leukocytosis. OBJECTIVE: To document the clinical course and autopsy findings of the fatal cases in Dublin. DESIGN: To study the clinical, autopsy, microbiologic, and toxicologic findings from the 8 fatal cases in Dublin. RESULTS: In Dublin, there were 6 men and 2 women who were fatally involved in the epidemic, with the mean age being 34 years (range, 22-51 years). The injection site inflammations involved the buttock (n = 4), leg, iliac region, arm, and a Portacath site. At autopsy, the local lesions were ulcerated, swollen, and indurated but were inconspicuous in 2 patients. All the deceased had pulmonary edema. There were pleural effusions in 7, 2 of whom had pericardial effusions. Five had prominent left ventricular subendocardial hemorrhages. Five had splenomegaly. Microscopy showed pulmonary edema and a granulocytic reaction mainly in the spleen, marrow, and myocardium. Toxicology showed a range of narcotic drugs in the toxic or fatal range. Clostridium novyi type A, a fastidious toxin-producing anaerobe, was identified in 2 cases. CONCLUSION: The clinicopathologic findings of a local inflammatory lesion followed 7 to 14 days later by a rapidly fatal systemic illness are consistent with the effect of exotoxin produced by organisms growing in the local inflammatory site. Clostridium novyi-derived exotoxin is the likely cause of such a syndrome, although the fastidious organism was isolated from only 2 of 8 cases (from none of the 14 surviving patients and from only 13 of 60 cases in Scotland). In the setting of an epidemic, the toxic and fatal range blood levels of narcotics are unlikely to explain these events, and no other candidate organism could be isolated. The heroin is likely to have come from Afghanistan, but local contamination at a putative distribution site in the United Kingdom is more likely than international terrorism to be the initiating factor.

[The lipid peroxidation processes and the antioxidant system in the dynamics of an experimental Pseudomonas aeruginosa intoxication]. / Sostoianie protsessov perekisnogo okisleniia lipidov i antioksidantnoi sistemy v dinamike éksperimental'noi sinegnoinoi intoksikatsii.

Lipid peroxidation and antioxidant defense processes have been studied over the course of experimental Pseudomonas aeruginosa intoxication in albino rats injected with a lethal dose of exotoxin A. The development of intoxication is associated with intensification of lipid peroxidation, manifested by accumulation of malonic dialdehyde and diene conjugates and decreased peroxide resistance of erythrocytes. Superoxide dismutase and catalase activities were inhibited and the concentration of vitamin B dropped. Injection of antioxidant alpha-tocopherol or antihypoxant gutimine at the late stage of intoxication did not notably modify the studied parameters.

Congenital streptococcal toxic shock syndrome with absence of antibodies against streptococcal pyrogenic exotoxins.

Congenital infection with group A beta-hemolytic streptococcus was complicated by toxic shock syndrome in a neonate. We hypothesize that the severity of the clinical syndrome was related to the streptococcal pyrogenic exotoxin in the absence of corresponding antibodies. The outcome may have been favorably influenced by the antibodies to streptococcal pyrogenic exotoxin present in the immunoglobulins given as treatment.

[The acute toxicity of a bacterial insecticidal preparation containing a beta-exotoxin]. / Prouchvane na ostrata toksichnost na bakterialen insektitsiden preparat, sudurzhasht beta-ekzotoksin.

The acute toxicity of a new Bulgarian bioinsecticide preparation is determined, produced on the basis of Bacillus thuringiensis containing 0.1% beta-exotoxin by oral, dermal, inhalational and intraperitoneal introduction in experimental animals. The evaluation of the toxicity is performed by a complex of toxicometric, integral, haematologic and pathologicoanatomic methods according to the WHO and USA criteria for studying the safety of the microbic agents for plant protection. It is already established that the preparation introduced orally in dose 10,000 mg.kg-1 (1.6.10(11) cell kg.-1 10 micrograms.kg-1 beta exotoxin), applied dermally in dose 6000 mg.kg-1 (9.6.10(10), 6 micrograms.kg-1 beta exotoxin) and in concentration 300 mg.m-3 (4.8.10(10) cell m-3, 300 micrograms.m-3 beta exotoxin) provokes no lethality, intoxication and changes in the integral, haematologic and pathologicoanatomic studies of test animals. LD50 at intraperitoneal introduction in white rats is 387.20 mg (6.2.10(10), kg-1, 387.2 micrograms kg-1 beta exotoxin) for male and 364.0 mg kg-1 (0.58.10(9) kg-1 364.0 micrograms kg-1 beta exotoxin) for female animals. The investigations point out that according to rate of acute toxicity the bacterial preparation containing 0.1% beta exotoxin is referred to the low toxic substances and reveals no danger for acute oral, dermal and inhalational poisonings when the regulations for production and use are observed.

[Mechanism of action of Pseudomonas aeruginosa exotoxin on the macroorganism (experimental studies)]. / Mekhanizm deistviia ékzotoksina Pseudomonas aeruginosa na makroorganizm (éksperimental'nye issledovaniia).

Some problems of the pathogenic action of P. aeruginosa exotoxin on the body have been experimentally studied. Under the conditions of intoxication produced by P. aeruginosa exotoxin pronounced functional disturbances in the main parameters of central hemodynamics and changes in the coagulation properties of the blood and in the free-radical peroxidation of lipids have been found to occur. The manifestation of pathological changes has been shown to have certain specific features in different organs and to depend on the time elapsed after the introduction of exotoxin into the animals.

[Veno-occlusive disease of the liver: report of 2 cases in the northeast of Brazil]. / Doenca veno-oclusiva do fígado: registro de dois casos no nordeste do Brasil.

Two cases of veno-occlusive disease of the liver (VOD) are reported in eleven and twelve-year-old children. The number of Brazilian cases of this entity amounts to five, with the addition of the present cases. One patient was in a subacute stage (central hepatic fibrosis) and had her diagnosis based on hepatic biopsy and venography; the other one was necropsied in a cirrhotic stage. Aspects concerning differential diagnosis with other regional hepatic disease, as well as the currently known geographic distribution and etiologic possibilities of VOD were reviewed.

Age-related susceptibility of mice to ocular challenge with Pseudomonas aeruginosa exotoxin A.

We studied the responses of mice to ocular challenge with purified exotoxin A from Pseudomonas aeruginosa in 5-, 10-, 16-, 21-, and 30-day-old animals. In the absence of trauma, injection of 3 to 6 microgram of exotoxin per mouse beneath the fused eyelids of 5-day-old Swiss-Webster mice resulted in death of all animals within 24 h. Administration of 1.5, 0.75, and 0.375 microgram of exotoxin per mouse resulted in 24-h mortality rates of 50, 22, and 20%, respectively. Additional deaths were recorded throughout the next 4 days. Similar lethality results were obtained with 10-day-old animals that received equivalent amounts of exotoxin beneath the fused eyelid and in these experiments, the 72-h 50% lethal dose was 0.49 microgram of exotoxin per mouse. Mice that were 16 and 21 days old, whose eyelids were open, each received from 0.375 to 15 microgram of exotoxin topically applied to the surface of a wounded cornea. Cataracts were observed within 1 week in both groups, and none of the animals that received the higher concentrations of toxin died. Young adult (30-day-old) animals also received from 1.8 to 15 microgram of exotoxin topically on the surfaces of wounded corneas. Corneal swelling and slight opacity were observed at 24 h and within 1 month; 80% of these mice had cataracts of the ocular lens.