Bites by the Monocled Cobra, Naja kaouthia, in Chittagong Division, Bangladesh: Epidemiology, Clinical Features of Envenoming and Management of 70 Identified Cases.

AbstractWe describe 70 cases of monocled cobra (Naja kaouthia) bite admitted to Chittagong Medical College Hospital, Bangladesh. The biting snakes were identified by examining the dead snake and/or detecting N. kaouthia venom antigens in patients' serum. Bites were most common in the early morning and evening during the monsoon (May-July). Ligatures were routinely applied to the bitten limb before admission. Thirty-seven patients consulted traditional healers, most of whom made incisions around the bite site. Fifty-eight patients experienced severe neurotoxicity and most suffered swelling and pain of the bitten limb. The use of an Indian polyvalent antivenom in patients exhibiting severe neurotoxicity resulted in clinical improvement but most patients experienced moderate-to-severe adverse reactions. Antivenom did not influence local blistering and necrosis appearing in 19 patients; 12 required debridement. Edrophonium significantly improved the ability of patients to open the eyes, endurance of upward gaze, and peak expiratory flow rate suggesting that a longer-acting anticholinesterase drug (neostigmine) could be recommended for first aid. The study suggested that regionally appropriate antivenom should be raised against the venoms of the major envenoming species of Bangladesh and highlighted the need to improve the training of staff of local medical centers and to invest in the basic health infrastructure in rural communities.

A new Pan African polyspecific antivenom developed in response to the antivenom crisis in Africa.

Currently there is a crisis in the supply of antivenom for treatment of snake bite in sub-Saharan Africa. Commercial pressures have resulted in the reduction or even cessation of production of antivenom by European manufacturers while continued production of antivenom in Africa has been threatened by the privatisation of the only remaining company based in Africa. As a consequence, there has been an increase in snake bite morbidity and mortality in many African countries. Two Latin American antivenom manufacturers have agreed to produce antivenom suitable for Africa, using venoms from the species which are of the greatest medical importance in sub-Saharan Africa. Preclinical in vivo assays of neutralising potency demonstrated that a new Pan African antivenom produced in Colombia compared favourably with the existing commercial monospecific and polyspecific antivenoms. This new antivenom, and a similar product being manufactured in Costa Rica, are now candidates for clinical testing at an appropriate site in Africa.

Venom detection kits in the management of snakebite in Central province, Papua New Guinea.

The bites of six species of venomous elapid snakes in Central Province Papua New Guinea produce similar clinical syndromes. Optimal management of envenomed patients involves the use of monospecific antivenom. In this study, Venom Detection Kits (VDKs) (CSL Diagnostics, Melbourne) were used to try to make a specific diagnosis in envenomed patients at their admission. VDKs detected venom in admission bite site swabs from 39 to 46 patients (85%). Thirty-eight of these patients were shown to have been bitten by taipans. In all cases where venom was detected by the VDK, this correlated with subsequent laboratory enzyme immunoassay results. Selective use of VDKs in Central Province could allow more widespread use of monospecific antivenoms and produce considerable financial savings.

Purified chick embryo cell rabies vaccine: economical multisite intradermal regimen for post-exposure prophylaxis.

The standard six-dose intramuscular (i.m.) rabies post-exposure vaccine regimen using a new purified chick embryo cell (PCEC) vaccine was compared with two economical multisite intradermal (i.d.) PCEC regimens, a multisite i.m. PCEC schedule and a subcutaneous regimen using a suckling mouse brain (SMB) rabies vaccine manufactured in Thailand. The neutralizing antibody results for the four-site and eight-site i.d. and the standard i.m. PCEC regimens were similar over 3 months. A three-site i.m. PCEC regimen had no advantage. The SMB vaccine gave the lowest antibody levels. Human rabies immune globulin therapy significantly increased the GMT of all groups on day 7, unlike equine antirabies serum (EARS). Both antisera suppressed antibody responses to PCEC on days 14 and 28. Three generalized reactions probably related to EARS were the only serious side effects. An eight-site i.d. PCEC vaccine regimen proved as immunogenic as the routine i.m. schedule and, if implemented as post-exposure prophylaxis, would be the cheapest widely available tissue culture vaccine regimen. The protective efficiency should now be tested in patients bitten by rabid animals.

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.

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.

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.