Danai Bunnag

Dexamethasone proves deleterious in cerebral malaria. A double-blind trial in 100 comatose patients.

High-dose dexamethasone was compared with placebo in a double-blind trial involving 100 comatose patients with strictly defined cerebral malaria. The two treatment groups, whose members were six to 70 years old, proved comparable on admission. There were eight deaths in the dexamethasone group and nine in the placebo group (no significant difference; P = 0.8); at post-mortem examination the brain showed features diagnostic of cerebral malaria in all but one patient who died. Dexamethasone prolonged coma among the survivors: the interval between the start of treatment and the full recovery of consciousness was 63.2 +/- 5.9 hours (mean +/- S.E.M.) in the dexamethasone group, as compared with 47.4 +/- 3.2 hours in the placebo group (P = 0.02). Complications, including pneumonia and gastrointestinal bleeding, occurred in 26 patients given dexamethasone and 11 given placebo (P = 0.004). Only five patients had neurologic sequelae. Results were similar in a subgroup of 28 children six to 14 years old. Dexamethasone is deleterious in cerebral malaria and should no longer be used.

EFFECT OF PRIMAQUINE ON GAMETOCYTES OF PLASMODIUM FALCIPARUM IN THAILAND

Sm,—Mr Ledingham and his colleagues (May 31, p. 1168) reported interesting findings on central rewarming using a modified Sengstaken tube in ansesthetised dogs. The rate of rewarming will, to some extent, depend upon the integrity of autonomic reflexes which tend to restore normal body temperature. Anaesthetic agents disrupt normal temperature regu’ lation, and it is not surprising that the temperature of the control animals did not rise during the four hour study, notwithstanding the radiant heat bulb. From the temperature curves shown of one rewarmed dog, the high skin temperature seen when the core temperature was only 35°C, highlights this point. The technique would appear to be of great value in the type of case described, where a patient is effectively poikilothermic as a result of traumatic or drug induced brain dysfunction, but the response may be different in hypothermia induced by exposure to low ambient temperature in otherwise normal people.

Dynamic alteration in splenic function during acute falciparum malaria

Plasmodium-infected erythrocytes lose their normal deformability and become susceptible to splenic filtration. In animal models, this is one mechanism of antimalarial defense. To assess the effect of acute falciparum malaria on splenic filtration, we measured the clearance of heated 51Cr-labeled autologous erythrocytes in 25 patients with acute falciparum malaria and in 10 uninfected controls. Two groups of patients could be distinguished. Sixteen patients had splenomegaly, markedly accelerated clearance of the labeled erythrocytes (clearance half-time, 8.4 +/- 4.4 minutes [mean +/- SD] vs. 62.5 +/- 36.5 minutes in controls; P less than 0.001), and a lower mean hematocrit than did the patients without splenomegaly (P less than 0.001). In the nine patients without splenomegaly, clearance was normal. After institution of antimalarial chemotherapy, however, the clearance in this group accelerated to supernormal rates similar to those in the patients with splenomegaly, but without the development of detectable splenomegaly. Clearance was not significantly altered by treatment in the group with splenomegaly. Six weeks later, normal clearance rates were reestablished in most patients in both groups. We conclude that splenic clearance of labeled erythrocytes is enhanced in patients with malaria if splenomegaly is present and is enhanced only after treatment if splenomegaly is absent. Whether this enhanced splenic function applies to parasite-infected erythrocytes in patients with malaria and has any clinical benefit will require further studies.

High rate of Plasmodium vivax relapse following treatment of falciparum malaria in Thailand.

Within two months of treatment for falciparum malaria, Plasmodium vivax infections developed in 58 (33%) of 174 patients who had received a quinine or quinidine regimen and in 46 (32%) of 145 patients who had received mefloquine with inpatient follow-up of more than six weeks. The time to vivax relapse was significantly longer after mefloquine treatment (median 47 days, range 30-65) than after quinine or quinidine treatment (21 days, 15-36; p less than 0.0001). All patients remained outside areas of malaria transmission. These findings suggest a very high rate of double infection in Thailand with acute suppression of vivax by falciparum malaria, and warrant evaluation of radical therapy with primaquine in certain patients with acute falciparum malaria.

Do patients with cerebral malaria have cerebral oedema? A computed tomography study.

Computed tomography of the brain in 10 patients with severe cerebral malaria, 5 of whom died, showed evidence of cerebral oedema in only 2 fatal cases. Small areas of altered density were seen in 4 cases; these were not associated with focal neurological signs and were still visible in convalescent scans in 2 survivors. 4 patients, including 1 of the fatalities, had completely normal scans. Cerebral oedema may occur in severe cerebral malaria but is not a consistent feature of living patients and cannot, therefore, always be the cause of their coma.

The hyaluronidase activities of some Southeast Asian snake venoms

The hyaluronidase activities of venoms of snakes indigenous to Southeast Asia were investigated. With the exception of the venom of the Malayan krait Bungarus candidus, the elapid venoms had either little or no hyaluronidase activities, whereas the viperid venoms possessed considerable activity. A component of Russells viper venom with hyaluronidase activities had a mol. wt of approximately 14,000. Neither MP4, a monoclonal antibody raised against the purified Russells viper venom hyaluronidase toxin, nor a monospecific polyclonal antivenom neutralized the hyaluronidase activities of this purified hyaluronidase component of crude Russells viper venom. The Russells viper venom hyaluronidase activities was labile on heating and storage. The significance of these observations to envenomation and antivenom production is discussed.

High dose of primaquine in primaquine resistant vivax malaria

The efficacy of low dose chloroquine, characteristic pattern of relapse and the relapse rate in vivax malaria after high dose primaquine were investigated in 167 Thai patients. 87 patients were allocated at random to receive 300 mg, and 80 received 450 mg of chloroquine on the first day of admission. All patients in both groups showed a rapid response with comparable fever clearance times (27.3 vs. 26.1 h) and parasite clearance times (67.1 vs. 58.1 h). After recovery and clearance of parasitaemia, the patients were allocated at random (double blind) to receive 2 dosage regimens of primaquine, a daily dose of 15 mg or 22.5 mg for 14 d. Relapses in both groups occurred within 6 months; no patient relapsed beyond that period. The relapse rate in the primaquine 15 mg group was significantly higher than that in the 22.5 mg group (17.5% vs. 2.4%).

Comparison of oral artemether and mefloquine in acute uncomplicated falciparum malaria

Plasmodium falciparum malaria in Thailand is highly resistant to available antimalarials, and alternative drugs are needed urgently. Artemether is effective against falciparum malaria but associated with a high recrudescence rate. The proper dosage regimen remains to be defined. We have done a clinical trial comparing mefloquine 1250 mg in divided doses with oral artemether at 700 mg total dose given over 5 days in acute uncomplicated falciparum malaria. 46 patients, admitted to the Bangkok Hospital for Tropical Diseases, were randomised to receive either mefloquine (12) or artemether (34). Hospital follow-up was 28 days for the artemether group and 42 days for the mefloquine group. Oral artemether gave a significantly faster parasite clearance time than mefloquine (30 vs 64 h), and a significantly better cure rate (97 vs 64%) with fewer episodes of dizziness and vomiting. Oral artemether at 700 mg given over 5 days is effective and well tolerated. The cure rate with this regimen is higher than that reported by previous studies with 600 mg intramuscular artemether given over 5 days. Oral artemether can be considered as an alternative drug for multiple-drug-resistant falciparum malaria.

QUINIDINE IN FALCIPARUM MALARIA

Fourteen patients with falciparum malaria were successfully treated with oral quinidine. Twelve of these patients were followed for 35 days without recrudescence. In six patients the infection had already recrudesced after antimalarial treatment, which in two cases had included a full course of quinine. Quinidine caused no cardiotoxicity, although the electrocardiogram QTc interval was prolonged by more than 25% in four patients. In-vitro cultures from nine of these patients and a further seven patients with falciparum malaria showed that the minimum inhibitory concentration was consistently lower for quinidine than for quinine. Quinidine is an effective antimalarial drug for Plasmodium falciparum infections and may be more potent than quinine.

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.