Effects of malaria during pregnancy on infant mortality in an area of low malaria transmission.

Malaria during pregnancy reduces birth weight, and low birth weight is a major determinant of infant mortality. The authors estimated the impact of malaria during pregnancy on infant mortality in a Karen population living in Thailand. Between 1993 and 1996, a cohort of 1,495 mothers and their infants was followed weekly from admission of the mother to antenatal clinics until the first birthday of the infant. Both falciparum malaria and vivax malaria during pregnancy were associated with low birth weight but did not shorten gestation. Febrile illness in the week before delivery was associated with premature birth. Preterm and full-term low birth weight and fever in the week before delivery were associated with neonatal mortality. Maternal fevers close to term were also associated with the deaths of infants aged between 1 and 3 months, whereas no risk factors could be identified for deaths that occurred later in infancy. Thus, malaria during pregnancy increased neonatal mortality by lowering birth weight, whereas fever in the week before birth had a further independent effect in addition to inducing premature birth. The prevention of malaria in pregnancy and, thus, of malaria-attributable low birth weight should increase the survival of young babies.

Adverse effects in patients with acute falciparum malaria treated with artemisinin derivatives.

In prospective studies of acute uncomplicated, multidrug-resistant falciparum malaria on the western border of Thailand, the oral artemisinin derivatives were used alone in the treatment of 836 patients (artesunate 630, artemether 206), were combined with mefloquine (15-25 mg base/kg) in 2,826 patients, and mefloquine alone was used in 1,303 patients. The combined regimens of mefloquine plus an artemisinin derivative were associated with more side effects than those with an artemisinin derivative alone; acute nausea (31% versus 16%), vomiting (24% versus 11%), anorexia (51% versus 34%), and dizziness (47% versus 15%) (P < 0.001). Oral artesunate and artemether alone were very well tolerated. There was no difference in the incidence of possible adverse effects between the two drugs, and no evidence that either derivative caused allergic reactions, neurologic or psychiatric reactions, or cardiovascular or dermatologic toxicity. Blackwater fever occurred in three patients treated with mefloquine plus artesunate regimens. Oral artesunate and artemether are safe and well tolerated antimalarial drugs.

Artesunate and mefloquine in the treatment of uncomplicated multidrug-resistant hyperparasitaemic falciparum malaria.

Oral artesunate is the most effective treatment for uncomplicated hyperparasitaemia in falciparum malaria. To assess the contribution of mefloquine to therapeutic efficacy in an area endemic for mefloquine-resistant Plasmodium falciparum, an open randomized comparison of a 5 d course of oral artesunate (total dose 12 mg/kg) with and without a single dose of mefloquine (25 base mg/kg) was conducted in 100 adults and children with uncomplicated hyperparasitaemia (> 4% parasitized red blood cells). Both regimens were well tolerated and gave equally rapid clinical responses (84% of patients were aparasitaemic and 96% were afebrile within 48 h), but the recrudescence rate assessed at day 42 was 6% in those receiving artesunate with mefloquine compared to 36% in those receiving artesunate alone (adjusted hazard ratio 7, 95% confidence interval [95% CI] 2-32; P < 0.01). In addition, the efficacy of a 7 d course of artesunate, with and without the addition of mefloquine, was monitored in 178 patients who were not part of the randomized comparison. The failure rate was again lower in those receiving artesunate and mefloquine--7% (95% CI 2-13) compared with 26% (95% CI 8-44) in patients treated with artesunate alone. An oral regimen of 5 d or more of artesunate, together with mefloquine (25 mg/kg) given on day 2, is an effective treatment for uncomplicated hyperparasitaemic falciparum malaria in this area of high level multidrug resistance.

Artesunate versus artemether in combination with mefloquine for the treatment of multidrug-resistant falciparum malaria.

To compare the therapeutic efficacy of oral artesunate and artemether in combination with mefloquine for the treatment of multidrug resistant malaria, a trial was conducted in 540 adults and children on the Thai-Myanmar border. Three regimens were compared: artesunate (4 mg/kg/d for 3 d), artemether (4 mg/kg/d for 3 d), both in combination with mefloquine (25 mg/kg), and a single dose of mefloquine (25 mg/kg). The artesunate and artemether regimens gave very similar clinical and parasitological responses, and were both very well tolerated. There was no significant adverse effect attributable to the artemisinin derivatives. Fever and parasite clearance times with mefloquine alone were significantly longer (P < 0.001). After adjusting for reinfections the failure rates were 13.9% for the artesunate combination, 12.3% for the artemether combination and 49.2% for mefloquine alone (P < 0.0001; relative risk 3.8 [95% confidence interval 2.6-5.4]). Mefloquine should no longer be used alone for the treatment of multidrug resistant falciparum malaria in this area. Three-day combination regimens with artesunate or artemether are well tolerated and more effective.

Estimation of plasma and urinary catecholamines in Guillain-Barré syndrome.

Serial estimation of plasma nor-epinephrine (PNE), 24 hours urinary vanilmandelic acid (VMA) and plasma cortisol was made in 25 adult patients of Guillain-Barré syndrome. Healthy adult age and sex matched volunteers served as controls. The mean level of PNE, VMA and plasma cortisol in controls was 1.07 +/- 0.50 ng/ml, 2.81 +/- 1.18 mg/24 hours and 12.9 +/- 3.10 micrograms/100 ml, respectively. In cases of Guillain-Barré syndrome with autonomic dysfunction the mean level of PNE, VMA and plasma cortisol was 3.34 +/- 2.47 ng/ml, 7.98 +/- 5.71 mg/24 hours and 27.25 +/- 4.94 micrograms/100 ml on the day of admission while in cases of Guillain-Barré syndrome without autonomic dysfunction it was 1.09 +/- 0.32 ng/ml, 3.04 +/- 2.22 mg/24 hours and 11.8 +/- 4.2 micrograms/100 ml, respectively. An increase in circulating PNE, VMA and plasma cortisol was demonstrated in patients of Guillain-Barré syndrome with autonomic dysfunction presenting as hypertension and tachycardia. The maximum rise of 284% (PNE) and 253% (VMA) occurred at the height of paralysis. The elevated levels fell to near control values at the time of significant recovery, and glucose tolerance tests improved. It is suggested that increased levels of catecholamines and cortisol contributed to the development of dysautonomia as these levels were within normal limits in patients of Guillain-Barré syndrome without autonomic dysfunction.