O. Walker

Prognostic risk factors and post mortem findings in cerebral malaria in children

We have examined the possible risk factors for poor prognosis in cerebral malaria in 61 Nigerian children in an area of high malaria transmission. The level of coma, decerebrate rigidity, hypoglycaemia, and high urea levels were indicators of poor prognosis. Pyrexia, vomiting, and anaemia did not influence prognosis. Post-mortem findings suggest gross cerebral oedema and raised intracranial pressure in 4 of 7 cases with petechial haemorrhages and small focal necrosis (Durcks granuloma).

Innate resistance to new antimalarial drugs in Plasmodium falciparum from Nigeria

The rapid dissemination of chloroquine-resistant Plasmodium falciparum in West Africa has been well documented and represents a significant health threat to autochthonous populations. The methodical development of alternative chemotherapeutic agents demands that dispensing new antimalarial drugs (mefloquine, halofantrine, and artemisinine [qinghaosu]) be closely monitored in order to protect their clinical utility. Indeed, mefloquine-resistant strains of P. falciparum have been reported. We present data from experiments in vitro on the innate resistance of P. falciparum isolates to mefloquine as well as a disturbing observation of transient resistance to artemisinine. The implications for the extended efficacy of these new antimalarial drugs are addressed.

An open randomized comparative study of intramuscular artemether and intravenous quinine in cerebral malaria in children

We have compared a multi-dose intramuscular regime of artemether against the standard intravenous quinine treatment for cerebral malaria in an open randomized study. Parasite clearance time, fever clearance time, and time to recover from coma were similar in the 2 groups of patients. Although the mortality rate was lower in the artemether group, the difference was not statistically significant. There was no toxic reaction of note in the artemether group. We therefore conclude that, because of its ease of administration and good toxicity profile, artemether is more suited for use in the rural regions of malaria endemic areas, where monitoring facilities may be minimal, compared to quinine which is potentially toxic.

The relationship between the response of Plasmodium falciparum malaria to mefloquine in African children and its sensitivity in vitro

The clinical efficacy of two doses of mefloquine (15 and 25 mg/kg body weight) was evaluated in 85 children suffering from acute symptomatic falciparum malaria. The cure rate on day 28 was 100% in both groups. There was no significant difference (P > 0.05) in the mean parasite and fever clearance times in both groups (48.5 +/- 14.6 and 32.0 +/- 12.7 h respectively for the 25 mg/kg group and 49.0 +/- 15.1 and 30.0 +/- 13.3 h respectively for the 15 mg/kg group). There was also no significant difference (P > 0.05) in these values between children with hyperparasitaemia (53.6 +/- 11.1 and 36.0 +/- 17.0 h respectively) and those without hyperparasitaemia (49.1 +/- 13.6 and 31.8 +/- 14.6 h respectively). Recurrence of parasitaemia was observed after day 30 in 2 patients in the 15 mg/kg group and in 1 patient in the 25 mg/kg group. In vitro, 3 of 21 isolates showed reduced susceptibility to mefloquine, with minimum inhibitory concentrations (MIC) > 67 nM/litre. The MIC and 50%, 90% and 99% inhibitory concentrations were 200.8, 6.27, 31.7 and 119.6 nM/litre respectively. Four of 22 isolates were resistant to chloroquine (MIC > 108 nM/litre). Isolates that showed low sensitivity to mefloquine in vitro were sensitive to chloroquine in vitro, and the 4 that were resistant to chloroquine were sensitive to mefloquine. Irrespective of MIC and dose of mefloquine, parasitaemia cleared in all subjects in 96 h or less.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical efficacy of mefloquine in children suffering from chloroquine-resistant Plasmodium falciparum malaria in Nigeria.

One hundred and thirteen children with symptomatic uncomplicated falciparum malaria were treated with either chloroquine 25 mg/kg body weight over 3 d (51 subjects) or mefloquine 25 mg/kg body weight single dose (62 subjects). The cure rate in the chloroquine group was 65% and in the mefloquine group 100%. 14 patients with chloroquine-resistant falciparum malaria (7 RI, 6 RII and one RIII) were successfully treated with mefloquine. The clearance times of parasitaemia and fever were 60 +/- 21.5 h and 24.7 +/- 10.1 h respectively in the chloroquine-sensitive group and 52.3 +/- 18.2 h and 24.5 +/- 23.7 h respectively in the mefloquine group. In the chloroquine-resistant group treated successfully with mefloquine, these clearance times were 44.0 +/- 8.9 and 24.0 h respectively. The only remarkable adverse reaction in the chloroquine group was pruritus which occurred in 7 subjects. Abdominal pain and diarrhoea (8 subjects) and dizziness (3 subjects) were the only important adverse reactions in the mefloquine group. It is concluded that, despite previous reports of primary reduced susceptibility to mefloquine in vitro of some West African isolates of Plasmodium falciparum, this drug may be useful in the treatment of both chloroquine-sensitive and chloroquine-resistant falciparum malaria in West Africa.

Evaluation of the clinical efficacy and safety of halofantrine in falciparum malaria in Ibadan, Nigeria

Fifty subjects with acute symptomatic uncomplicated falciparum malaria were treated orally with halofantrine hydrochloride 500 mg 6 hourly for 3 doses if their body weight was 40 kg and above, or 8 mg/kg body weight 6 hourly for 3 doses if their weight was below 40 kg. Parasitaemia cleared in all subjects within 72 h. There was recurrence of parasitaemia in 9 subjects after day 14, and retreatment with halofantrine resulted in prompt clearance of parasitaemia in all but one of these patients. The mean clearance times of parasitaemia, fever and other symptoms were 33.6 +/- 13.0 h, 20.7 +/- 15.3 h, and 35.0 +/- 10.7 h respectively. Minor gastrointestinal side effects occurred in 2 subjects and pruritus in 7 subjects. The pruritus was mild in all but one subject. Haematological and biochemical indices were not adversely affected by treatment except in one subject in whom liver enzymes were elevated before treatment and more than doubled following treatment.

Artemether in moderately severe and cerebral malaria in Nigerian children

Intramuscular artemether was compared with intramuscular sulfadoxine-pyrimethamine in Nigerian children with moderately severe malaria requiring parenteral therapy. Artemether produced significantly shorter parasite and fever clearance times but a higher parasite recrudescence rate than sulfadoxine-pyrimethamine. There was no significant difference in their initial parasitological cure rates--100% for artemether, 98% for sulfadoxine-pyrimethamine. In a separate study intramuscular artemether was compared with intravenous quinine in children with cerebral malaria. There was no significant difference between the 2 drugs in parasite and fever clearance times, time to regain consciousness, or recrudescence rate. There was an overall mortality of 16.7%, with 12% in the artemether group and 21% in the quinine group. Artemether was well tolerated. There was no abnormal change in haematological and biochemical features monitored and there was no adverse clinical reaction. These results show that artemether is a potentially useful drug for moderate and severe malaria and its place in the chemotherapy of malaria deserves further study.

Hyperparasitaemia: not a reliable indicator of severity or poor prognosis in falciparum malaria in children in endemic African countries

Hyperparasitaemia as an indicator of severity or poor prognosis in falciparum malaria and response to oral antimalarial therapy were evaluated in an outpatient study of 77 consecutive African children from an endemic area. At presentation, clinical illness was graded as mild in 37, moderate in 14 and severe in 26. There was no evidence of renal, hepatic or cerebral complications. Clinical response to oral antimalarial drugs was characterized by rapid and uneventful recovery from illness in all but one patient who required hospital admission with prompt clearance of parasitaemia and fever within 96 hours. It is concluded that greater than 5% parasitaemia may be well tolerated by semi-immune African children. Semi-immune subjects with hyperparasitaemia and no other evidence of severe or complicated disease in an endemic area may well be treated with oral antimalarials providing the infecting strain is fully sensitive to the drug chosen and the drug is rapidly absorbed.

Parenteral sulphadoxine-pyrimethamine (Fansidar): an effective and safe but under-used method of anti-malarial treatment.

One hundred and eighteen patients with acute falciparum malaria were randomized into treatment with either intramuscular or oral sulfadoxine-pyrimethamine (Fansidar, Roche) and the results were compared with those from 68 patients treated in parallel with chloroquine. Parasitological cure rate was 97% with oral sulfadoxine-pyrimethamine, 95% with the injection, and only 63% with chloroquine. The time for the disappearance of parasitaemia in sensitive cases was the same with oral and intramuscular sulfadoxine-pyrimethamine and shorter than with chloroquine. Side effects occurred in only 3 of the patients treated with intramuscular sulfadoxine-pyrimethamine compared with 8 of those treated with the tablets and 13 of those treated with chloroquine. The results showed that intramuscular sulfadoxine-pyrimethamine is as effective as, and probably better tolerated than, the oral drug. Increasing failure of response to chloroquine in Nigeria was also demonstrated.

The sensitivity of Plasmodium falciparum to chloroquine and amodiaquine in Ibadan, Nigeria.

An extended in vivo test of the sensitivity of Plasmodium falciparum to antimalarial drugs in Nigerian children showed no evidence of resistance to chloroquine and amodiaquine. However, the results of a small number of in vitro tests suggest a decreased sensitivity of the parasite to chloroquine when compared with the results of earlier studies in the same locality.