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Pioneers of anti-venomous serotherapy: Dr Vital Brazil (1865-1950).

Dr Vital Brazil was a great humanitarian and pioneer of medical science. His main work arose from his concern with poisonous snakebite accidents to labourers working the land. Vital Brazil estimated that, at the beginning of this century, deaths due to crotaline snakebites in the State of São Paulo, Brazil, were nearly 3000 per year, representing a mortality rate of about 25%, the majority being due to bothropic envenomation. After reading a report of Calmette's anti-Naja serum, Vital Brazil raised monovalent serum against the venom of Bothrops jararaca and the venom of Crotalus durissus terrificus. In 1989 this led to the first demonstration of the specificity of anti-venomous serum and later, the first production of polyvalent serum for therapeutic use. As Director of the newly founded Institute Butantan in São Paulo, Vital Brazil was actively engaged in every aspect of serotherapeutic treatment. This included organizing a unique system of exchanging anti-ophidic serum for snakes as well as a wide-ranging teaching programme. His many outstanding contributions to the fields of immunology, public health, toxinology and herpetology required not only a very high level of observational, deductive and practical ability but also an unswerving vision and sense of duty; this was allied to great administrative skill and exceptional energy.

Antivenins↗

[Vital Brazil].

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[Vital Brazil].

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Brazil↗

Vital Brazil.

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Brazil↗

Randomized comparative trial of three antivenoms in the treatment of envenoming by lance-headed vipers (Bothrops jararaca) in São Paulo, Brazil.

In São Paulo City, Brazil, 121 patients with moderately severe envenoming by Bothrops snakes (principally B. jararaca) were randomized for treatment with Brazilian polyspecific Bothrops antivenoms: Instituto Butantan (39 patients), Instituto Vital Brazil (41), Fundação Ezequiel Dias (FUNED) (41). The initial dose was four ampoules (40 ml) in 89 patients with less severe envenoming and eight ampoules (80 ml) in 32 patients with more severe envenoming. A second dose of four ampoules was required in 20 patients. Patients receiving the three antivenoms were comparable in all respects before treatment. There were no deaths. The majority showed rapid clinical improvement, resolution of local envenoming, cessation of bleeding and restoration of blood coagulability. No differences in the efficacy of the three antivenoms were revealed by clinical or laboratory observations, including measures of haematological, haemostatic and biochemical abnormalities. Twelve patients developed abscesses (Butantan 1, Vital Brazil 6, FUNED 5) and seven developed local necrosis (3,1,3). Of 88 patients followed up 20-30 days after the bite 33 (37.5%) still had symptoms or signs of local envenoming, especially swelling. Early (anaphylactic) reactions were unexpectedly frequent after all three antivenoms but were significantly more frequent with Butantan (87%) than with Vital Brazil (37%) or FUNED (56%) antivenoms (p < 0.001). A possible explanation was the higher total protein content and percentage immunoglobulin of Butantan antivenom. The doses of antivenom recommended in Brazil and used in this study may be unnecessarily high, resulting in an unacceptably high incidence of reactions. Results of the study should prompt a critical re-evaluation of antivenom production techniques and dosage recommendations in Brazil.

Adolescent↗

Comparison of the potency of three Brazilian Bothrops antivenoms using in vivo rodent and in vitro assays. BIASG (Butantan Institute Antivenom Study Group).

Three Brazilian polyspecific Bothrops antivenoms were compared using standard W.H.O. rodent in vivo and in vitro assays of their ability to neutralize the principal venom activities of pooled whole Bothrops jararaca venom. On a volume basis, the antivenoms were equally effective in neutralizing lethal activity in mice, and there were only minor differences in their ability to neutralize venom-induced haemorrhage, necrosis and procoagulant activity. Antivenom efficacy in neutralizing defibrinogenation varied. However, when equal amounts of antivenom IgG were compared, it was found that the FUNED antivenom best neutralized lethality, haemorrhage, necrosis and fibrinogen clotting activity. Vital Brazil and FUNED antivenoms were equally effective in neutralizing plasma coagulant activity but Vital Brazil antivenom was the more effective in neutralizing defibrinogenation.

Animals↗

Clinical and epidemiological features of definitive and presumed loxoscelism in São Paulo, Brazil.

A retrospective study analysed 359 proven or presume cases of loxoscelism seen at the Hospital Vital Brazil, Instituto Butantan, São Paulo, Brazil, between 1985 and 1996. The spider was identified in 14%. The bites occurred predominantly in the urban areas (73%) between September and February. Patients > 14 years were commonest inflicted (92%) and 41% were bitten while getting dressed. Only 11% sought medical care within the first 12 hours post bite. Cutaneous loxoscelism was the commonest form presenting (96%); commonest manifestations were: pain (76%), erythema (72%), edema with enduration (66%), ecchymosis (39%). Skin necrosis occurred in 53% of patients, most frequently seen on trunk, thigh and upper arm, and when patients seek medical care more than 72 hours after bite. Local infection was detected in 12 patients (3%). Hemolysis was confirmed in 4 cases (1.1%). Generalised cutaneous rash, fever and headache were also observed in 48% of the total of patients. None of them had acute renal failure or died. Treatment usually involved antivenom administration (66%), being associated with corticosteroids (47%) or dapsone (30%). Presumptive diagnosis of loxoscelism may be established based on clinical and epidemiological findings. Further investigations are required to prove the value of antivenom and other treatment schedules.

Adolescent↗

Mygalomorph spider bites: a report on 91 cases in the state of São Paulo, Brazil.

From 1966 to 1991 91 cases of bites due to mygalomorph spiders were recorded at the Hospital Vital Brazil, Instituto Butantan, São Paulo, Brazil, representing less than 1% of all spider bites. The diagnosis was confirmed by positive identification of the spider involved. Envenoming is generally mild, the main symptom is local pain, and there is minor oedema and erythema. The data confirm the assumption that these nonaggressive spiders pose no health problem.

Adult↗

Wolf spider bites in São Paulo, Brazil: a clinical and epidemiological study of 515 cases.

Data obtained from 515 victims of bites of wolf spiders (family Lycosidae) who were attended in Vital Brazil Hospital, São Paulo City, Brazil, in a 5-year period (1979-1983) were analysed. Bites were more frequent in males (56%). All age groups were involved. Foot and hand were the preferential sites of bite (79%), and pain, generally mild, was the predominant symptom (83%). No local necrosis, a severe complication described in the previous literature, was detected, suggesting that those old cases were due to misdiagnosed Loxosceles spider bites. Specific antivenom was employed in only three cases which is evidence that physicians do not consider wolf spider bites to be severe.

Adolescent↗

[Snake bite epidemiology in the last 100 years in Brazil: a review].

We review 30 studies on snake bites in Brazil, published from 1901 to 2000, and conclude that epidemiological analyses conducted in the last 100 years are based on the same variables already identified by Vital Brazil in his pioneering report, i.e., characteristics of the individuals prone to snake bites, the bites themselves, and treatment. The original epidemiological profile was also maintained over the years and indicates that such accidents are more frequent among male farm workers in the 15-49-year age bracket, affecting mainly the lower limbs, and caused by snakes from genus Bothrops.

Adolescent↗

Envenoming by Bothrops jararaca in Brazil: association between venom antigenaemia and severity at admission to hospital.

The association between the clinical severity of Bothrops jararaca envenoming at admission and serum venom and plasma fibrinogen concentrations before antivenom administration is reported in 137 patients admitted to Hospital Vital Brazil, Instituto Butantan, São Paulo, Brazil, between 1989 and 1990. Other variables such as age, gender, site of the bite, use of tourniquet and the time interval between the bite and start of antivenom therapy, spontaneous systemic bleeding, and the 20 minute whole blood clotting test (20WBCT) at admission showed no association with either severity or serum venom antigen concentration (SVAC). Mean SVAC in patients with mild envenoming was significantly lower than in the group with moderate envenoming (P = 0.0007). Patients with plasma fibrinogen concentrations > 1.5 g/L had a lower mean SVAC than patients with plasma fibrinogen concentrations < or = 1.5 g/L (P = 0.02). Those admitted with a tourniquet in place had significantly higher plasma fibrinogen concentrations than those without a tourniquet (P = 0.002). A multiple logistic regression model showed independent risk factors for severity: bites at sites other than legs or forearms, SVACs > or = 400 ng/mL, and the use of a tourniquet. Rapid quantification of SVAC before antivenom therapy might improve initial evaluation of severity in B. jararaca bites.

Adolescent↗

Prognostic factors for local necrosis in Bothrops jararaca (Brazilian pit viper) bites.

The prognostic factors related to envenoming are not very well known. This study aims to identify prognostic factors for necrosis in envenoming by Bothrops jararaca. We analysed 779 medical records of patients bitten by B. jararaca and treated at the Hospital Vital Brazil, Butantan Institute, São Paulo, Brazil, between 1982 and 1990: 111 cases with necrosis were compared with the remaining cases. The length of the snake, the bite site, the month of the accident, pain, oedema, ecchymosis, blisters, systemic bleeding, shock, and the use of tourniquet were statistically associated with the presence of necrosis (P < 0.05) in the univariate analysis. The size of the snake, the bite site (leg and finger), the sex of the patient, the month of the accident, systemic bleeding, and the use of tourniquet were independent prognostic factors within the variables tested in the multivariate analysis. The size of the snake was the most important independent prognostic factor related to the presence of necrosis.

Adolescent↗

Envenoming by the South American pit viper Bothrops neuwiedi Wagler.

Between 1975 and 1992, 18 cases of envenoming by Bothrops neuwiedi presented at the Hospital Vital Brazil, in São Paulo. Most of these cases were male (67%) and most had been bitten during the day (83%), between November and May (83%), either on the foot/ankle (50%) or hand (39%). Most (72%) of the cases arrived at the hospital 1-6 h after the bite. All presented with pain and most (83%) had oedema, but fewer had ecchymosis (50%), necrosis (17%), abscess (5%) and/or systemic blood-coagulation disorders (12%). Polyspecific Bothrops antivenom was administered to 16 (89%) of the patients. The results of B. neuwiedi bites therefore appear very similar to those of the much better known B. jararaca, even in terms of the gravity of the envenoming. Impairment in blood coagulation, however, seems less frequent among those bitten by B. neuwiedi than in those bitten by B. jararaca.

Adolescent↗

Prognostic factors for amputation in the case of envenoming by snakes of the Bothrops genus (Viperidae).

The prognostic factors for amputation following envenoming by snakes of the Bothrops genus were identified from the medical records of 3139 patients. Each of these patients had been bitten by Bothrops sp. and treated in the Hospital Vital Brazil, in São Paulo, Brazil, between 1981 and 1990. The 21 (0.67%) of the patients who had undergone amputation were compared with the 3118 who had not, with respect to the characteristics of the accident, the snake, the victim, the local and systemic manifestations of the envenoming and the treatment. There was an association between amputation and the month of the accident, the time of day when the accident happened, the length of the attacking snake, the anatomical region bitten, systemic bleeding and renal failure. Patients bitten in the fingers, during the cooler months, between 00.00 and 12.00 hours and/or by snakes > 60 cm in length, who developed blisters and abscesses at the site of the bite, systemic bleeding and/or renal failure underwent amputation more frequently than the others (P < 0.05 for each).

Adolescent↗

Search of intravascular hemolysis in patients with the cutaneous form of loxoscelism.

Haptoglobin assay, a highly sensitive method to detect intravascular hemolysis was carried out in the sera of 19 patients referred to Hospital Vital Brazil with the cutaneous form of loxoscelism in order to investigate the occurrence of mild intravascular hemolysis. Data from this series did not show decreased levels haptoglobin, ruling out intravascular hemolysis in these patients with cutaneous form of loxoscelism.

Adolescent↗