Intraleucocyte malaria pigment in asymptomatic and uncomplicated malaria

While malaria pigment or haemozoin is known to be an end product of haemoglobin digestion by the malaria parasite, its clinical significance is just beginning to be elucidated. We have studied the distribution of intraleucocyte malaria pigment in 92 children, consisting of 32 children with asymptomatic malaria, 32 children with mild or uncomplicated malaria and 28 children with no malaria. Over 90% of children in each of the three groups had pigment-containing monocytes and the numbers of pigment-containing monocytes were not significantly different between the three groups. While over 90% of children in both the asymptomatic malaria and uncomplicated malaria groups had pigment-containing neutrophils, 71.4% of the no malaria group had such neutrophils. The numbers of pigment containing neutrophils was highest in the uncomplicated malaria group, followed by the asymptomatic malaria group with the no malaria group having the least numbers. The pigmented neutrophil: monocyte ratio followed the same pattern. It was concluded that the number of pigment-containing neutrophils and the pigmented neutrophil:monocyte ratio may be a marker of the severity of malaria infection when one considers the conditions: no malaria, asymptomatic malaria and mild malaria. Further work to verify this hypothesis across the full spectrum of the manifestations of malaria infection is needed.     

Mortality and morbidity from malaria after stopping malaria chemoprophylaxis

Gambian children who had received malaria chemoprophylaxis for a variable period of time during their first 5 years of life were followed to determine whether they experienced a rebound in mortality or in morbidity from malaria during the period after chemoprophylaxis was stopped. The risk of dying between the ages of 5 years, when chemoprophylaxis was stopped, and 10 years was no higher among children who had received chemoprophylaxis with Maloprim (pyrimethamine plus dapsone) for some period during their first 5 years of life than among children who had received placebo (21 vs. 24 deaths) and the beneficial effect of chemoprophylaxis on mortality observed during the first 5 years of life was sustained. The incidence of clinical attacks of malaria during the year after medication was stopped was significantly higher among children who had previously received Maloprim for several years than among children who had previously received placebo. However, at the end of this year, there was no significant difference in spleen rate, parasite rate or packed cell volume between the 2 groups of children. Thus, stopping chemoprophylaxis after a period of several years increased the risk of clinical malaria but did not result in a rebound in mortality in Gambian children. However, the number of deaths recorded was small, so a modest effect on mortality cannot be excluded.     

1998 malaria therapy

A review of the principal antimalarial drugs is presented as the basis for specific recommendations on the treatment of malaria. These are adapted to conditions in Switzerland. Considering that the majority of Plasmodium falciparum infections imported into this country are acquired in areas with a high prevalence of chloroquine resistance, mefloquine is generally considered the first-line drug for the treatment of uncomplicated falciparum malaria. For severe tropical malaria, or if parasitaemia exceeds 2%, quinine remains the drug of choice. The pharmacological decision must estimate the risk of drug-resistant malaria and consider the clinical condition, possible intolerance and drug interactions. Prognosis is always difficult in falciparum malaria; hence hospitalization is always strongly recommended if the course is in doubt and if close monitoring of the patient is not otherwise guaranteed. In hospital, ancillary treatment (e.g. exchange transfusion) must receive timely consideration. Special considerations must be borne in mind with regard to the treatment of malaria in children and during pregnancy.     

The epidemiology of malaria

Epidemiologists have recently paid greater attention than in the past to the epidemiology of clinical malaria as opposed to the epidemiology of malarial infection. This change of emphasis has been stimulated in part by the need for better clinical definitions of malaria in the evaluation of control measures such as insecticide-treated materials and malaria vaccines. Methods of determining mortality from malaria and of defining severe and uncomplicated malaria have been devised. The limited data available indicate that malaria-attributable mortality and the incidence of severe malaria do not increase with an increase in the entomological inoculation rate above a threshold value, an observation that has important implications for the likely long-term effects of attempts to contain malaria through vector control. Study of the epidemiology of severe malaria in Africa has shown different epidemiological patterns for the two most frequent forms of this condition: cerebral malaria and severe malarial anaemia. Severe malarial anaemia is seen most frequently in areas of very high malaria transmission and most frequently in young children. In contrast, cerebral malaria predominates in areas of moderate transmission, especially where this is seasonal, and it is seen most frequently in older children. Study of patients with uncomplicated malaria has established the relationship between fever and parasite density and has demonstrated ways of defining fever thresholds. Algorithms have been developed to help in the diagnosis of malaria in the absence of parasitological confirmation but this approach has proved difficult because of the overlap in symptoms and signs between malaria and other acute febrile illnesses such as pneumonia.     

Clinical pharmacology and malaria

The role of clinical pharmacology in improving the prevention and treatment of malaria is reviewed. A series of general and specific issues is discussed, concentrating on risk-benefit and cost-effectiveness. The techniques of clinical pharmacokinetics play an important role in the optimal use of drugs and this is illustrated by studies on quinine and proguanil. In discussing amodiaquine toxicity, the role of the pharmacologist and the chemist in designing out drug toxicity lends hope for producing a new generation of antimalarial drugs.     

Seizures in cerebral malaria

The authors proposed a new application of helical CT, namely, CT-ventriculography that can obtain 2D and 3D images of different cardiac phases. CT-ventriculography could assess wall motion, systolic thickening and chamber volume. From a single breath hold helical CT 50-rotation), about 500 transaxial slices were obtained by applying overlapping reconstruction (0.1 pitch, 0.08 sec = 0.2 mm interval). All transaxial slices were recordered to separate different cardiac phases. Then, long and short axial 2D tomograms and 3D images in different cardiac phases were reformatted. CT-ventriculography is a promising new application for the assessment of heart function.     

Fetal circulation and malaria

OBJECTIVE: To quantity the fetal vascular changes during flare-up, and to evaluate the sensitivity and the specificity of Doppler indices for the prediction of acute fetal distress at the end of the pregnancy. METHOD: Every day of flare-up the umbilical resistance (Rp), cerebral resistance (Rc), cerebro-placental ratio (CPR = Rc/Rp), and hypoxia index (HI = delta % CPR x crisis duration) were calculated. RESULTS: Twenty-three pregnancies were investigated at St Laurent du Maroni Hospital (French Guiana). During flare-ups the Doppler placental resistance increased (placental disorder), cerebral resistance decreased (vasodilation), CPR decreased (flow redistribution toward the brain), and HI increased. An abnormal CPR (< 1) was associated with abnormal fetal heart rate (FHR) in 61.5% of the cases, a CPR > 1 was associated with a normal FHR in 80% of the cases. (sensitivity: 80%, specificity 61%). A CPR < 1 was associated with one of the abnormalities (abnormal FHR, cesarean section, abnormal Apgar) in 71% of the cases, a CPR > 1 was associated with normal delivery in 55% of the cases (sensitivity: 71.4%, Specificity 55%). A HI higher than 150 was associated with abnormal FHR in 75% of the cases, a HI < 150 was associated with normal FHR in 90% of the cases (sensitivity: 89%, specificity: 77%). Lastly the combination (HI > 150 + CPR < 1) was associated with abnormal FHR in 80% of the cases, 1 or 2 of these parameters were associated with normal FHR in 84.6% of the cases (sensitivity: 80%, specificity: 84%). The minimum CPR and the HI during malaria flare-up can be used to predict acute fetal distress at delivery.