Chaisin Viravan

Prediction, prevention, and mechanism of early (anaphylactic) antivenom reactions in victims of snake bites.

Victims of snake bites are often subjected to cutaneous or conjunctival hypersensitivity testing before being given antivenom. None of 12 early (anaphylactic) reactions was predicted by these tests in 25 Nigerian and Thai patients. The incidence and severity of early reactions was the same whether antivenom was given by intravenous injection over 10 minutes or diluted and given as an intravenous infusion over 30 minutes. Although antivenom activated complement in vitro, there was no evidence of complement activation or formation of immune complexes in patients bitten by snakes who were treated with antivenom, whether or not they developed early reactions. Higher doses of antivenom might induce the complement activation and formation of immune complexes (aggregates) that have been observed during the clinically more severe reactions associated with homologous immunoglobulin treatment.

ECONOMICAL MULTIPLE-SITE INTRADERMAL IMMUNISATION WITH HUMAN DIPLOID-CELL-STRAIN VACCINE IS EFFECTIVE FOR POST-EXPOSURE RABIES PROPHYLAXIS

An economical post-exposure regimen of Mérieux human diploid-cell-strain vaccine (HDCSV) was compared with Semple vaccine (SV), the most widely used vaccine in Asia. 155 patients bitten by animals proved to be rabid received either conventional courses of SV (34 severe and 43 mild cases) or HDCSV, 0.1 ml intradermally, at eight sites on day 0, at four sites on day 7, and at one site on days 28 and 91 (36 severe and 42 mild cases). All severely bitten patients were given equine anti-rabies serum (EARS), 80 IU/kg on day 0. There were no deaths from rabies in either group. Follow-up was 97.5% at 1 year and 93% at 2 years. 88% of patients given HDCSV alone had detectable neutralising antibody on day 7 in contrast to 2% given SV alone. Antibody persisted until 1 year in all sera tested from HDCSV patients in contrast to only 48% of SV sera. The high dose of EARS resulted in pronounced suppression of response to HDCSV. There were no serious systemic side-effects but local side-effects were significantly more common in the SV group. The multiple-site intradermal HDCSV regimen was at least as effective as SV. The amount of HDCSV used was 30% of the conventional dose.

Factors contributing to fatal snake bite in the rural tropics: analysis of 46 cases in Thailand

Records of 46 cases of fatal bites by identified snakes from 15 provincial hospitals throughout Thailand contained sufficient information for detailed analysis. Bungarus candidus and Calloselasma rhodostoma were each responsible for 13 deaths, Naja kaouthia for 12, Vipera russelli for 7 and B. fasciatus for one. Major causes of death among elapid victims were respiratory failure (26) and complications of prolonged mechanical ventilation (10), and among viper victims shock (12), intracranial haemorrhage (9), complications of local wound necrosis (7) including tetanus (2), and renal failure (2). Factors contributing to fatal outcome included inadequate dose of antivenom (15 cases), misidentification of the snake leading to use of the wrong antivenom (12), problems associated with mechanical ventilation (10), and delayed arrival in hospital after traditional (herbal) treatment (10). Similar problems have been identified in other tropical countries. Education of medical staff and the patient population at highest risk could reduce snake bite mortality.

AN ECONOMICAL REGIMEN OF HUMAN DIPLOID CELL STRAIN ANTI-RABIES VACCINE FOR POST-EXPOSURE PROPHYLAXIS

Vaccine regimens using 0.1 ml human diploid cell strain vaccine (HDCSV) given intradermally (id) in single and multiple sites, or with aluminum hydroxide adjuvant given subcutaneously (sc), were compared with the regimens of HDCSV and Semple vaccine currently suggested by WHO. Some groups were also given human rabies-immune globulin (HRIG). Neutralising antibody titres were monitored for 3 months. Antibody was detected earliest in subjects given 0.1 ml HDCSV id at each of eight sites. The highest antibody titres from day 14 onwards were found after intramuscular (im) administration of HDCSV, but the multiple-site id regimen, which requires only one quarter of the volume of vaccine required for the im regimen, gave similar results, provided that a booster was given on day 91. This finding suggests that a treatment schedule based on this regimen would be suitable for post-exposure prophylaxis. Adjuvanted vaccine gave similar results to the same amount of antigen given id. Semple vaccine produced the lowest titres. HRIG, given at the high dose of 40 IU per kg, suppressed the antibody response to some of the regimens.

Sulphormethoxine in chloroquine-resistant falciparum malaria in Thailand.

Abstract The long-acting sulphonamide, sulphormethoxine, has proved very effective in patients acutely ill with chloroquine-resistant falciparum malaria in Thailand. In a single dose of 1000 or 1500 mg., sulphormethoxine alone radically cured eleven out of eighteen patients (61%). A lower dose (250 mg.) of sulphormethoxine combined with a single dose of 12·5 or 25 mg. pyrimethamine cured eleven out of fifteen patients (73%). But the clinical response in these two groups was slow. A combination of 1000 mg. sulphormethoxine and 1500 mg. chloroquine base cured eleven of thirteen patients (85%). A single dose of 1000 mg. sulphormethoxine with 50 mg. pyrimethamine cured seventeen of nineteen patients (90%) and the response was rapid. Toxic effects were notably absent. Although these drugs have proved effective in chloroquine-resistant falciparum malaria, the risk of extending drug resistance should prompt caution in adopting such combinations for mass control therapy.

Arboreal green pit vipers (genus Trimeresurus) of south-east Asia: bites by T. albolabris and T. macrops in Thailand and a review of the literature

In Thailand 29 patients were proved to have been bitten by arboreal green pit vipers: 24 by Trimeresurus albolabris and 5 by T. macrops. They were studied in order to define the clinical effects of envenoming, to characterize the haemostatic abnormalities and assess the efficacy of Thai Red Cross antivenom. T. macrops caused only local painful swelling, neutrophil leucocytosis and thrombocytopenia. T. albolabris caused more severe envenoming with local blistering and necrosis, shock, spontaneous systemic bleeding, defibrination, thrombocytopenia and leucocytosis. There was no evidence of disseminated intravascular coagulation, but fibrinolytic activity was increased. Platelet function was normal. The product of admission venom antigen concentration and the delay between bite and admission was significantly higher in defibrinated patients than in those without severe coagulopathy. Antivenom (5 ampoules intravenously) restored blood coagulability, but there was persistent venom antigenaemia, associated in some cases with recurrent coagulopathy. The literature on bites by south Asian green pit vipers of the genus Trimeresurus is reviewed; these bites are common medical problems and causes of morbidity. The identification of individual species is difficult, but may be important if antivenom is to be improved and used appropriately.

MULTI-SITE INTRADERMAL AND MULTI-SITE SUBCUTANEOUS RABIES VACCINATION: IMPROVED ECONOMICAL REGIMENS

Neutralising antibody responses to six post-exposure regimens of human diploid cell strain rabies vaccine with or without human rabies immune globulin (HRIG) were studied in 98 patients. The total amount of vaccine used was 22-34% of that required by conventional regimens. Vaccine was given at multiple sites intradermally or subcutaneously with or without adjuvant. Antibody was detectable within 7 days of the first dose in all subjects only in the groups given 0.1 ml intradermally at 8 sites. From day 14 onwards all groups showed an excellent antibody response; there was little difference between the various regimens. Suppression of the response to 8-site intradermal vaccination by a large dose of HRIG could be prevented by giving the second dose of vaccine on day 7 rather than day 14.

Efficacy and tolerability of a sequential, artesunate suppository plus mefloquine, treatment of severe falciparum malaria.

Thirty patients with severe falciparum malaria were each given a total of 1600-mg artesunate suppository over three consecutive days followed by 1250 mg mefloquine per os, divided into two doses which were given 12 h apart. All patients were admitted for 28 days to the Bangkok Hospital for Tropical Diseases, so that the efficacy and tolerability of the treatment could be assessed. All the patients showed clinical improvement, with mean (S.D.) parasite and fever clearance times of 50.4 (13.0) and 70.7 (44.9) h, respectively. Two patients with unrousable coma (Glasgow coma score < or = 8) on admittance regained consciousness 46 and 48 h post-treatment. One other patient had acute renal failure and required dialysis. Most patients (80%) were initially hyperparasitaemic, with a mean density of 184,344 parasites/microliters blood. No deaths occurred. Efficacy was evaluated in 25 of the patients. The cure rate 28 days post-treatment was 92%. None of the patients had major adverse effects although two had tenesmus and passed stools immediately after each suppository was administered. A fresh suppository had to be inserted when this occurred. The results indicate that artesunate suppositories followed by oral mefloquine constitute a well-tolerated regimen with a high cure rate. The combination is suitable as an alternative treatment for severe malaria, particularly in children. Further, large-scale studies are required.

Treatment of acute, uncomplicated, falciparum malaria with oral dihydroartemisinin

A clinical trial of oral dihydroartemisinin for the treatment of acute, uncomplicated, falciparum malaria involved 53 adult patients in Thailand. Each received a total dose of 480 mg over 7 days (120 mg given immediately, followed by 60 mg/day) after being admitted to the Hospital for Tropical Diseases in Bangkok for 28 days. Most (92%) completed the 28-day follow-up but four patients left the hospital early, for reasons unrelated to their treatment. Most patients showed clinical improvement 1-3 days after starting treatment and none suffered from serious adverse reactions. The cure rate was 90% (44/49). The mean (S.D.) parasite-clearance time was 40.4 (14.1) h and the mean fever-clearance time was 37.0 (30.2) h. Seven patients had a brief increase in parasitaemia after initiation of treatment but subsequent counts declined dramatically. Five patients who failed treatment (RI response) were successfully treated with quinine plus tetracycline for 7 days. No RII or RIII responses were observed. These findings indicate that treatment with oral dihydroartemisinin is effective and well tolerated, and that dihydroartemisinin may be suitable as an alternative treatment for acute, uncomplicated, falciparum malaria. Comparisons with other conventional antimalarial drugs in a large, double-blind, randomized trial and studies of dihydroartemisinin in combination with other, long-acting antimalarials are needed.

Randomised trial of mefloquine-tetracycline and quinine-tetracycline for acute uncomplicated falciparum malaria

The combination of mefloquine plus tetracycline was compared with quinine plus tetracycline in a randomised therapeutic trial in 102 patients with acute uncomplicated falciparum malaria in Thailand. Quinine plus tetracycline is considered the standard treatment for the highly drug-resistant strains of P. falciparum found in this area. Fifty patients received mefloquine (750 mg given immediately, followed by 500 mg 6 h later) with tetracycline and 52 patients received quinine (600 mg every 8 h for seven days) with tetracycline. Tetracycline was administered to both groups in doses of 250 mg four times daily. All patients were admitted to the hospital for 28 days to exclude re-infection. Ninety-three patients completed the study; nine patients left prior to completion of follow-up for reasons unrelated to their treatment. Cure rates for the two groups were 94% (44/47) for mefloquine plus tetracycline and 98% (45/46) for quinine plus tetracycline. Parasite and fever clearance times were shorter for the group treated with mefloquine but the differences were not statistically significant. Nearly all patients (94%) treated with quinine developed cinchonism compared with only 12% treated with mefloquine; all other symptoms following treatment were similar. Thirteen patients (26%) treated with quinine also developed delayed primary attacks of P. vivax during the follow-up period; none developed in the patients treated with mefloquine. These results support the contention that the combination of mefloquine plus tetracycline is equally effective and less toxic than quinine plus tetracycline for treatment of acute uncomplicated falciparum malaria in areas requiring combination therapy for drug resistance.