Dangerous reactions to treatment of onchocerciasis with diethylcarbamazine.

Nine Nigerians with severe onchocerciasis who were treated with diethylcarbamazine developed clinical changes, ranging in severity from mild itching to distress, cough, and syncope. Physiological changes (fever, tachypnoea, tachycardia, or hypotension) were seen in eight. In five patients the systolic blood pressure fell by more than 25 mm Hg, and one patient collapsed on attempting to sit up. Circulating eosinophils decreased profoundly in all cases, reaching their lowest levels just before or during the clinical and physiological changes. A fall in serum complement (c3) accompanied the reaction but there was no fall in antibody titre. Diethylcarbamazine probably acts on the parasite's cuticle, thus exposing it to the body's defence mechansims. The reaction coincides with the death of microfilariae, and the accompanying physiological changes may be so severe, even in generally healthy patients, the treatment should perferably be started in hospital.

Poisoning by bites of the saw-scaled or carpet viper (Echis carinatus) in Nigeria.

The Saw-scaled or Carpet Viper (Echis carinatus) whose range extends from Senegal to Bengal probably bites and kills more people than any other species of snake. One hundred and fifteen patients with poisoning caused by its bite were studied in the savanna region of Nigeria, where victims of this snake may occupy 10 per cent of hospital beds. Patients showing no signs of envenoming were excluded. All patients had local swelling at the site of the bite. Other features included local blistering (13 per cent), local necrosis (11 per cent), incoagulable blood (93 per cent), and spontaneous systemic bleeding (57 per cent). There was evidence of disseminated intravascular coagulation in all cases; fibrinogen was severely depleted, fibrin degradation products were increased (mean 1711 +/- 904 micron per ml), but significant thrombocytopenia (less than 103 000 per mm3) was seen in only ten severe cases. Clotting factors V, VIII, II and XIII were depleted, while X and VII were usually normal. Fibrinolytic activity was rarely increased, so it seems likely that a procoagulant action (direct activation of prothrombin) is principal effect of E. carinatus venom on blood coagulation in man. Development of the haemostatic defect was observed as early as 75 minutes and as late as 27 hours after the bite. Spontaneous haemorrhage is clinically the most important effect of E. carinatus venom, causing the five deaths in this series. The relative importance of procoagulant and haemorrhagic components of the venom in causing haemorrhage is discussed. Complement activation via the classical and alternative pathways may have contributed to vascular damage. Mortality was reduced from the untreated level of between 10 and 20 per cent to 2.8 per cent in a group of 107 patients treated with 10 to 110 ml of specific antivenom. The dose was controlled using a simple clotting test. Blood coagulability was restored in two to 39 (mean 12) hours after the first dose of antivenom. Immediate-type serum reactions were observed in 21 per cent of cases. Additional treatment included blood transfusion for patients in haemorrhagic shock and ealry surgical débridement of necrotic tissue at the site of the bite.

Disseminated intravascular coagulation caused by the carpet viper (Echis carinatus): trial of heparin.

Heparin has been advocated for the treatment of poisoning by Echis carinatus, a snake whose venom causes disseminated intravascular coagulation. Fourteen patients with proven E. carinatus bite who had incoagulable blood were treated with specific Echis antivenom. Seven of them were also given low-dose heparin, initially 50 units/kg body weight by i.v. injection, followed by 10 units/kg/h by i.v. infusion for 22 h. Response to treatment was assessed clinically and by repeated tests of blood coagulation. All patients showed a rapid return to normal blood coagulability after treatment and the heparinized group were not significantly different in any respect from the group given antivenom alone. Heparin did not reduce the local effects of envenoming. There appears to be no place for heparin in the treatment of E. carinatus poisoning provided that potent antivenom is available. The in vivo results were supported by in vitro studies in which it was found that Echis-induced thrombin was less sensitive to the inhibitory effect of heparin than physiological thrombin.

Pathophysiologic studies in human rabies.

Six patients with proved rabies were studied with a combination of clinical, physiologic and pathologic technics. Three were given a type of intensive care but died with evidence of respiratory failure. Although circulatory failure did not develop in any of the six patients, three had supraventricular arrhythmias: interstitial myocarditis was found in one of these and rabies virus was isolated from the myocardium of another. Inspiratory muscle spasm was the dominant clinical feature in all cases. This occurred as part of the hydrophobic response and followed stimulation of the upper respiratory tract and skin. Hydrophobia may represent an exaggerated respiratory tract irritant reflex with associated arousal. Later in the course of the disease, various patterns of periodic and ataxic breathing were observed. Widespread brain stem encephalitis was discovered at autopsy, with particular involvement of the neighborhood of the nucleus ambiguous in two of three patients examined. In one patient cerebral metabolism was grossly abnormal, with greatly reduced cerebral oxygen consumption suggesting irreversible brain damage. Respiratory and circulatory disturbances may well be immediate causes of death in patients with rabies, but the present studies reemphasize the severity of the encephalitis which remains the ultimate barrier to survival. In the developing countries in which rabies is still a major problem and in which the cost precludes intensive care, the clinical management of rabies can aim only to reduce suffering by heavy sedation.

Silicosis among grindstone cutters in the north of Nigeria.

Many of the grindstones used in Nigerian homes are quarried from sandstone in a small group of villages near Kano in the extreme north of the country. Of an unselected group of 126 stonecutters from two of these villages 49 were found to have radiographic evidence of silicosis, with progressive massive fibrosis in 17. Those with silicosis had worked longer in the quarries than 77 whose radiographs showed no evidence of silicosis. Sixty-three per cent of the silicotics had respiratory symptoms, the commonest being breathlessness on moderate exertion. Cough was the earliest symptom in 42%. Only 35% had abnormal physical signs in the cardiorespiratory system, 18% had clearly reduced ventilatory capacity, and airways obstruction was evident in 16%. The prevalence of silicosis in these open-cast sandstone quarriers is unexpectedly high. This is probably explained by the intensity of exposure and the particular kind of sandstone being worked. Reduction of dust exposure in these quarries raises severe practical problems, but the inhabitants of this drought-ridden area can scarcely be expected to abandon their traditional livelihood.

Bronchial asthma in the Nigerian savanna region. A clinical and laboratory study of 106 patients with a review of the literature on asthma in the tropics.

One hundred and six asthma patients were studied in Zaria in the Nigerian savanna region. This group resembled hospital attenders in general in containing a disproportionately large number of immigrants from southern Nigeria and students undergoing higher education. Childhood asthma was rare. Asthma started after the age of 19 years in 69 per cent of patients. Twenty-seven per cent gave a history of rhinitis but none had had eczema. Twenty-two per cent gave a family history of asthma. Cutaneous hypersensitivity to house dust supported by a history of attacks being precipitated by dust was found in 41 per cent of patients. Asthma was worst in the rainy season in 45 per cent of patients. Mites were found in mattress dust samples; the mean count was 243 mites per g dust; Dermatophagoides farinae formed 86-6 per cent of the total mite population. The variability of airways obstruction averaged 50 per cent of maximum values for forced expiratory volume in the first second (FEV1) and peak expiratory flow (PEF). The median severity of airways obstruction measured as FEV1/VC per cent was four standard deviations below predicted normal. Eighty-seven per cent of patients were positive to prick skin tests with one or more allergens. The commonest reactions were to house dust (58 per cent), house dust mite (45 per cent) and Dermatophagoides farinae (44 per cent). Fifty-one per cent of a group of controls were also positive on skin testing but the pattern of responses was different from the asthmatic patients. This high proportion of reactors is explained by high allergen load. Serum IgE levels were lower in the asthmatics than in a group of healthy controls who showed the very high levels characteristic of some African populations. We suggest that the controls were protected from atopic disease by developing high blocking levels of non-specific IgE, perhaps in response to gut helminths. The clinical pattern of asthma in Zaria is compared with other countries in the tropical and temperate zones. The particular problems of treating asthma in developing tropical countries are discussed.

Demonstration during life of rabies antigen in humans.

In three cases of human rabies, in which the diagnosis was proved postmortem, rabies antigen was detected by direct immunofluorescence of frozen sections of facial skin. The antigen was thought to be in nerve fibers in association with hair follicles. Development of this technique might enable the establishment of a method for the diagnosis of human rabies during life.

Bites by the saw-scaled or carpet viper (Echis carinatus): trial of two specific antivenoms.

Echis carinatus is the most important cause of morbidity and mortality from snake bite in Nigeria and in many other parts of the world. Forty-six patients with systemic poisoning by this snake were given echis antivenom made either by the South African Institute for Medical Research (S.A.I.M.R.) or by Behringwerke (North and West African polyvalent antivenom). A simple test of blood coagulability was used to assess whether an adequate neutralizing dose of antivenom had been given. An average of 15.2 ml S.A.I.M.R. antivenom restored normal coagulability permanently in all 23 patients in one group, but in the other group receiving an average dose of 37.9 ml Behringwerke antivenom normal clotting resulted in only 18 out of 23 patients. Local tissue swelling was similar in both groups, but local necrosis occurred in three patients treated with Behringwerke antivenom and in none given S.A.I.M.R. antivenom.