Biochemical evidence of muscle injury in African children with severe malaria.
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Biomedical subjects
Publications and source records attributed to K D Miller.
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Magnetic resonance imaging (MRI) is constantly progressing as an important imaging modality for the evaluation of the cardiovascular system and vascular malformations. Due to its superior contrast resolution and sensitivity, MRI is able to differentiate between fat, muscle, bone, and vascular structures. It provides three-dimensional information without the use of ionizing radiation or invasive procedures. We evaluated 11 vascular malformations by MRI using Spin Echo T1 and T2 weighted images. MRI provided more information than computerized tomography, and, in many instances, obviated the need for angiography.
Although empirical regimens of parenteral chloroquine have been used extensively to treat severe malaria for 40 years, recent recommendations state that parenteral chloroquine should no longer be used because of potential toxicity. We studied prospectively the pharmacokinetics and toxicity of seven chloroquine regimens in 58 Gambian children with severe chloroquine-sensitive falciparum malaria. In all regimens the total cumulative dose was 25 mg of chloroquine base per kilogram of body weight. Chloroquine was rapidly absorbed after either intramuscular or subcutaneous administration (5 mg of base per kilogram every 12 hours), producing high peak blood concentrations but transient hypotension in 5 of 18 patients (28 percent). Intermittent intravenous infusion (5 mg of base per kilogram over 4 hours, repeated every 12 hours) also produced wide fluctuations in chloroquine levels, suggesting incomplete distribution from a small central compartment. Continuous infusion (0.83 mg of base per kilogram per hour for 30 hours) and smaller, more frequent intramuscular or subcutaneous injections of chloroquine (3.5 mg of base per kilogram every 6 hours) produced smoother blood-concentration profiles with lower early peak levels and no adverse cardiovascular or neurologic effects. Chloroquine given by nasogastric tube (initial dose, 10 mg of base per kilogram) was absorbed well, even in comatose children. We conclude that simple alterations in dosage and frequency of administration can give parenteral chloroquine an acceptable therapeutic ratio and reinstate it as the treatment of choice for severe malaria in areas where chloroquine resistance is not a major problem.
To determine whether infection with Loa loa could be prevented in temporary residents of endemic areas, we conducted a randomized, double-blind, placebo-controlled trial of diethylcarbamazine as a chemoprophylactic agent. Diethylcarbamazine (300 mg) or placebo was taken orally once a week by Peace Corps volunteers serving in Gabon, Cameroon, and the Central African Republic. The participants were assessed clinically and with serologic and parasitologic testing before and yearly during their two years of service. One hundred one persons satisfactorily completed the study. In Gabon (where exposure to the parasite was heaviest), 6 of 20 volunteers (30 percent) in the placebo group had clinical disease, as compared with none of 16 (0 percent) in the diethylcarbamazine-treated group (P less than 0.02). Of those taking placebo, 10 of 20 (50 percent) became seropositive for antifilarial IgG antibody, as compared with 2 of 16 (12 percent) in the drug-treated group (P less than 0.02). Exposure to the parasite appeared to be much lower among the 65 Peace Corps volunteers in Cameroon and the Central African Republic. No volunteer in either group in these countries had overt loiasis; 2 of 40 (5 percent) in the placebo groups in Cameroon and the Central African Republic seroconverted, as compared with none of 25 (0 percent) of those receiving diethylcarbamazine. Occasional nausea was the only symptom significantly associated with the prophylactic drug regimen. We conclude that diethylcarbamazine given orally once weekly can be an effective, acceptable chemoprophylactic agent to prevent loiasis in temporary residents of regions of Africa where Loa loa is endemic.
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Due to excellent soft tissue contrast and multiplanar imaging capability, MRI is assuming a major role in recognition, staging, and treatment planning of soft tissue and bone tumors. Direct sagittal, coronal, and axial images permit assessment of intraosseous and extraosseous extension of tumors and their relationship to the joints and neurovascular structures, and detection of "skip" lesions. MRI allows improved detection of recurrent tumors in the presence of non-ferromagnetic metallic implants as compared to CT. In the evaluation of soft tissue tumors, MRI is more sensitive than CT and allows differentiation among fat, muscle, tendon, bone, and vascular structures based on signal characteristics. Over a period of 18 months, 100 soft tissue masses and bone tumors were evaluated using MRI. Spin echo sequences with T1 and T2 weighted images were most valuable in differentiating normal and abnormal tissues. Calculated comparative measurements of relaxation times showed no reliable difference between benign and malignant tumors.
Selected findings from the Multicenter AIDS Cohort Study (MACS) of homosexual/bisexual men are reviewed. High risk sexual behaviors, the use of drugs/alcohol, condom use, and behavior change are addressed in a public health context. The potential significance of education/behavior modification programs as strategies for public health intervention emerges from these findings. Until there is a realistic timetable for vaccine availability and more effective chemotherapy, the MACS provides the opportunity to continue to study the effects of behavior change on the AIDS epidemic.
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Hypoglycaemia, defined as a plasma glucose concentration below 2.2 mmol/l, developed in 15 of 47 prospectively studied Gambian children with severe chloroquine-sensitive falciparum malaria. 5 of these hypoglycaemic children died compared with 1 in the normoglycaemic group (p = 0.02). In contrast to previous observations in quinine-treated adults, in whom hypoglycaemia was associated with hyperinsulinaemia, plasma concentrations of insulin were appropriately low and plasma ketones were high. Raised plasma concentrations of lactate and alanine suggested impairment of hepatic gluconeogenesis. In African children, hypoglycaemia is an important and treatable manifestation of severe malaria and is unrelated to antimalarial treatment.
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Chloroquine, in a single dose of 10 mg of base/kg, was given orally to Togolese children less than 5 years of age as primary therapy for Plasmodium falciparum malaria. A simplified World Health Organization in vivo method was used, as was a sequential analysis procedure for determining if the drug trial was a success or failure. A total of 178 children in 3 regions were treated; 174 (98%) responded successfully, which required a greater than or equal to 75% reduction in parasites by day 2 and elimination of parasites by day 7. All 4 failures had low blood levels of chloroquine and desethylchloroquine at day 7. A single dose of chloroquine for treating malaria can be considered for those areas of Africa where the efficacy of such therapy is documented, and where an antimalarial drug sensitivity monitoring system is operating.
Pyrimethamine-sulfadoxine has been associated with severe and fatal cutaneous reactions as well as transient liver damage. We report the case of a patient who died of progressive hepatic failure caused by pyrimethamine-sulfadoxine administration. In addition, we summarize reports made to the Food and Drug Administration since 1982 that focus on hepatotoxic reactions to pyrimethamine-sulfadoxine. We suggest that fatal hepatic injury can occur after treatment with pyrimethamine-sulfadoxine and that physicians who prescribe the drug should be aware of this possibility.
Acute intrapartum ethanol intoxication occurred in a chronic ethanol abuser. Continuous fetal heart rate monitoring revealed a pattern of fetal tachycardia, decreased variability and late and variable decelerations in association with a maternal serum ethanol level of 300 mg/dL. This case gives evidence of an association between very high maternal serum ethanol levels and acute fetal distress.
Loiasis in residents of endemic areas is generally manifested by microfilaremia, episodic angioedema, periocular migration of adult worms, modest eosinophilia, and variable antibody levels. In 20 temporary residents who acquired loiasis in West Africa, however, the clinical presentations were markedly different. Only three of the 20 had detectable microfilaremia. Furthermore, these patients often showed a state of marked immunological hyperresponsiveness manifested by very high titers of antibody to filariae, increased levels of serum IgE, and profound hypereosinophilia--to levels greater than 3,000/mm3 in 18 of the 20. These patients were also notable for the increased severity, frequency, and pruritic nature of their angioedema. Also, significant complications occurred in seven of the 20; one patient developed endomyocardial fibrosis and six, renal disease after treatment with diethylcarbamazine. Thirteen of the 20 developed subcutaneous nodules; adult parasites were recovered from three of five of these patients who underwent biopsy. All of the patients responded to therapy with diminution of their clinical symptoms and decreases in levels of eosinophils, IgE, and antibody to filariae.
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In 1982, the fixed combination of pyrimethamine and sulfadoxine (Fansidar) became available in the United States, and was recommended for use in travelers at risk of acquiring chloroquine-resistant Plasmodium falciparum. Prior to that time, no reports of severe cutaneous reactions had appeared in the medical literature despite widespread use for more than 8 years in both Europe and malarious areas of the developing world. In the fall of 1984, the Centers for Disease Control received reports of 4 cases of toxic epidermal necrolysis (including 3 fatalities) among Americans who had used pyrimethamine-sulfadoxine (PYR/SDX) for the prevention of malaria. Subsequent investigation into severe cutaneous reactions associated with the use of this drug by American travelers detected 24 cases of erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis. Twenty-three of the 24 patients concurrently used chloroquine. Seven patients died. No risk factors in the development of these reactions other than the use of PYR/SDX could be identified. Among American travelers, we estimate that these reactions occur in 1 per 5,000-8,000 users, and that fatal reactions occur in 1 per 11,000-25,000 users. This higher than expected incidence necessitates that the use of PYR/SDX for the prevention of malaria be reconsidered. In the United States it is now recommended that the routine weekly use of the drug be reserved for those travelers at highest risk of acquiring chloroquine-resistant P. falciparum, when alternate prophylactic regimens are not deemed appropriate.